![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, South Dakota
Received for publication
June 22, 2005
Accepted
November 7, 2005.
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
). However, a recent and controversial epidemiologic report outlined data linking diuretic use to the incidence of end-stage renal disease (Hawkins and Houston, 2005). The effect, if true, may be a consequence of potential detrimental effects of diuretics on GFR and RBF, which could augment the progression of pre-existing renal disease.
In addition, diuretic-induced alterations of renal hemodynamics limit the efficacy of these agents. For example, carbonic anhydrase inhibition (CAI) attenuates sodium reabsorption in the proximal tubule (PT), resulting in a diuretic effect; however, the diuretic effect is self-limiting, in part, because of a marked decrease in the GFR and RBF. The CAI-induced decreases of GFR and RBF are believed to be mediated through activation of tubuloglomerular feedback (TGF) (Tucker et al., 1978). An increase of sodium chloride delivery to tubular macula densa cells, as occurs after inhibition of proximal sodium reabsorption, stimulates the release of a putative chemical mediator that induces vasoconstriction of the adjacent afferent arteriole. An increase of resistance in the afferent arteriole reduces GFR and RBF, resulting in decreased filtration of sodium into the tubular lumen of that nephron, thus opposing the desired diuretic effect of drug treatment. Furthermore, these renal hemodynamic effects alter the bioavailability of the diuretics at their sites of action because the drugs must be filtered or actively secreted into the tubular lumen to inhibit sodium transport.
An additional concern regarding the use of diuretics relates to their concomitant effects on potassium. Diuretics that inhibit sodium reabsorption upstream of the collecting duct (i.e., PT, thick ascending limb of Henle's loop, or distal convoluted tubule) cause hypokalemia. In contrast, diuretics that block sodium reabsorption in the collecting duct, either through direct inhibition of sodium channels or through antagonism of aldosterone, inhibit the secretion of potassium.
Whereas diuretic therapy is generally effective, there are clinical situations in which relative diuretic resistance occurs. For example, loop diuretics are often less effective in heart failure patients (Brater, 1998), perhaps secondary to impaired renal hemodynamics and enhanced proximal tubular sodium reabsorption in this pathological condition (Kramer et al., 1999). In addition, resistance to diuretic therapy may develop during chronic treatment due to up-regulation of sodium transporters at the various tubular segments (Na et al., 2003; Kim, 2004).
In view of the limitations described above, it would be ideal to have a diuretic regimen that 1) inhibits sodium reabsorption at multiple tubular sites, including the PT, to offset the development of diuretic resistance; 2) does not cause significant perturbations of renal potassium handling; and 3) does not activate TGF-mediated reductions of RBF and GFR. Multiple agents may be required to achieve the ideal diuretic goals. In this study, we evaluated whether addition of an A1 adenosine receptor (A1AR) antagonist could offset the un-wanted effects of CAI while enhancing the desirable diuretic/natriuretic responses.
A1AR antagonists represent a novel class of agents for potential use in the treatment of hypertension and edema (Welch, 2002). Indeed, these drugs produced diuretic effects and blood pressure reductions in salt-sensitive (Nomura et al., 1995; Uehara et al., 1995) and genetically hypertensive rats (Kost et al., 2000). In addition, A1AR antagonists induced diuresis without worsening renal or cardiac function in a rat model of heart failure (Jackson et al., 2001). Interestingly, A1AR antagonists produced diuresis and natriuresis of greater magnitude than thiazide diuretics (Gellai et al., 1998) but without significant potassium wasting or reductions of RBF and GFR. Furthermore, clinical trials in a limited number of subjects demonstrated that A1AR antagonists produced natriuretic and hypotensive effects in essential hypertensive patients (van Buren et al., 1993) and attenuated the furosemide-induced decline of renal hemodynamic function in heart failure patients (Gottlieb et al., 2002). The effects seem to be mediated through blockade of tubular A1AR at multiple sites along the tubule and blockade of vascular A1AR in the afferent arteriole (Fig. 1). This is consistent with data indicating that adenosine is a potent vasoconstrictor of the afferent arteriole and, perhaps, the chemical mediator of TGF (Osswald et al., 1982).
|
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Surgical Procedures. On the day of the acute experiment, each rat was removed from its home cage, anesthetized with thiobutabarbital (Inactin; 100 mg/kg i.p.), and placed in dorsal recumbency on an isothermal pad (Braintree Scientific, Braintree, MA). Body temperature was monitored with a rectal thermal probe (model 8402-20; Cole-Parmer Instrument Co., Vernon Hills, IL), and temperature was maintained at approximately 37°C by adjustment of an over-head heat lamp. A short section of polyethylene tubing (PE-240) was placed in the trachea to facilitate respiration, and a PE-50 catheter was inserted into the right carotid artery to permit measurement of heart rate and mean arterial blood pressure (MABP) via a digital pressure analyzer (model BPA; Micro-Med Inc., Louisville, KY). The right jugular vein was cannulated with one PE-10 and two PE-50 catheters to permit infusion of saline, vehicle, or drug as appropriate. Isotonic 0.9% saline was infused at 2.5 ml/h via a jugular catheter throughout the acute experiment. A ventral midline incision was made through the skin and linea alba to expose the abdominal cavity. The intestines were slightly deflected using saline-soaked gauze to expose the left kidney. The left renal artery was carefully isolated from the surrounding fat and connective tissue, and a transit-time flow probe (model 1RB; Transonic Systems Inc., Ithaca, NY) was placed around the renal artery and attached to a flowmeter (model T206; Transonic Systems) to measure RBF. Space between the artery and probe was filled with sterile lubricating jelly as an acoustic couplant. The left ureter was carefully isolated and cannulated with PE-10 tubing to permit urine collection. Acute experimental protocols were initiated after a 60-min stabilization period.
Experimental Protocol 1: DPCPX and Acetazolamide. After a 60-min postsurgical stabilization period, rats were randomly selected to receive an infusion of the A1AR antagonist DPCPX at 10 µg/kg/min or its vehicle, DMSO, at 0.65 µl/min via the jugular venous PE-10 catheter. Given the relatively low infusion rate of DPCPX and its approximate 1000-fold selectivity for A1AR versus other adrenergic receptors (Fredholm et al., 2001), we believe this dose provided selective A1AR blockade in our study. In addition, a slow infusion rate for DPCPX and its vehicle was used because DMSO at higher infusion rates can induce hemolysis. In addition, a short section of narrow-lumen PE-10 catheter was used to reduce dead space in the line given the slow infusion rate. The infusion of DPCPX or DMSO was maintained throughout two consecutive 40-min clearance periods designated as period 1 and period 2. In period 1, there were 16 rats that received DPCPX and 17 rats that received its vehicle, DMSO. Urine volume was collected throughout the entire 40-min period, and MABP, heart rate, and RBF were recorded at 5-min intervals and then averaged over the 40 min. Data obtained in period 1 were subjected to statistical analysis to determine the effect of DPCPX alone compared with DMSO on the measured parameters. At the completion of period 1, rats within each group (DPCPX or DMSO) were randomly assigned to receive either acetazolamide (20 mg/kg i.v.) or its vehicle (2 M NaOH; 1 ml/kg i.v.) via a slow bolus injection lasting approximately 5 min. Completion of this bolus injection marked the beginning of period 2. Urine volume and hemodynamic parameters were measured throughout the 40-min period as described above. There were eight to nine rats in each of the four groups that received the following treatment regimen for period 1/period 2: DMSO vehicle and NaOH vehicle (Vh/Vh), DMSO vehicle and acetazolamide (Vh/AZ), DPCPX and NaOH vehicle (DP/Vh), and DPCPX and acetazolamide (DP/AZ). At completion of the study, rats were administered a lethal intravenous bolus injection of KCl, and the left kidney was removed and weighed.
|
). We estimated that 7.5 mg/l of L158809 in drinking water should provide a daily dose of greater than 0.3 mg/kg for the week leading up to the acute experiment. In a previous experiment, L158809 as a single oral dose of 0.3 mg/kg administered to conscious rats was shown to provide 75 to 85% blockade of ANGII- (0.1 µg/kg i.v. bolus) induced pressor responses with a 24-h duration of action (Siegl et al., 1992). Both the control and ARB-treated rats were surgically prepared as described above. After a 60-min postsurgical stabilization period, parameters such as urine excretion rate, MABP, and RBF were recorded over three consecutive 40-min collection periods. Period 1 served as the baseline period. At the completion of period 1, AZ (20 mg/kg i.v.) was administered by slow bolus injection, and parameters were measured for the following 40 min (period 2; AZ). During the final collection period (period 3; ANGII), rats were administered an intravenous infusion of ANGII at 15 ng/min to assess whether the ARB treatment regimen used in this study achieved adequate blockade of AT1 receptors. After period 3, rats were administered a lethal intravenous bolus injection of KCl, and the left kidney was removed and weighed.
Sample Analysis. Urine excretion rate was determined gravimetrically by weighing the collection tubes before and after each of the 40-min collection periods. Sodium and potassium concentrations were measured by flame photometry (model IL943; Instrumentation Laboratory, Lexington, MA). The urine excretion rate (UV), RBF, and excretion rates of sodium (UNaV) and potassium (UKV) were normalized to gram of kidney weight.
Statistical Analysis. Criterion for significance was p < 0.05. Data obtained during period 1 of the first protocol were compared using unpaired t test to assess the effect of DPCPX alone compared with that of DMSO. The interaction of DPCPX and AZ in protocol 1 was determined by two-factor, repeated measures ANOVA, where factor A = treatment group (i.e., plus/minus DPCPX), and the repeated factor B = period (i.e., plus/minus acetazolamide). Changes of period 1 to period 2 were analyzed by one-way ANOVA. Where appropriate, the ANOVA was followed up by a post hoc comparison with Fisher's least significant difference test. Data obtained in protocol 2 also were analyzed by two-factor, repeated measures ANOVA. In this case, factor A = treatment group (i.e., plus/minus ARB treatment), and factor B = period (i.e., baseline versus AZ versus ANGII). Where appropriate, the ANOVA was followed up by a post hoc comparison with Fisher's least significant difference test to assess the effect of AZ over the baseline period and the effect of ANGII over the AZ period. In addition, the AZ-induced change in parameters was compared between control and ARB-treated rats by t test. Analysis of data was performed with the Number Cruncher Statistical System (NCSS, Kaysville, UT).
Chemicals. Acetazolamide, DPCPX, DMSO, angiotensin II, and thiobutabarbital were purchased from Sigma-Aldrich (St. Louis, MO). L158809 was generously provided by the Merck Research Labs (Rahway, NJ).
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
The infusion of DPCPX or DMSO was continued into period 2, and rats in each group were further subdivided by random assignment to AZ or vehicle groups (Fig. 3). Of note, there were no "within-group" differences at baseline in the DPCPX or DMSO groups (post hoc; p > 0.05). In period 2, rats were administered a slow bolus of the CAI acetazolamide (Vh/AZ and DP/AZ) to block proximal tubular sodium reabsorption or its vehicle, 2 M NaOH (Vh/Vh or DP/Vh). AZ induced a significant increase of UNaV in both the DMSO-treated (Vh/AZ) and DPCPX-treated (DP/AZ) groups (Fig. 3). The absolute UNaV was significantly greater in the DP/AZ rats compared with Vh/AZ rats; however, the AZ-induced increase of UNaV (i.e., 
UNaV; period 2 minus period 1) was not significantly different between the two groups. This indicates that DPCPX and AZ have an additive effect on UNaV. Despite the increased UNaV in DP/AZ compared with Vh/AZ rats, the UKV was significantly lower in the DP/AZ group, and the AZ-induced increase of UKV was attenuated by more than 50% in the DPCPX group (Fig. 3). The diuretic response (i.e., increase of UV) to AZ was similar in the DMSO- (Vh/AZ) and DPCPX- (DP/AZ) treated rats (Fig. 4). In addition, AZ produced a significant and similar decrease of RBF in both the DMSO and DPCPX groups (Fig. 4). The observation that A1AR blockade with DPCPX failed to attenuate the RBF decrease induced by AZ lead us to perform the experimental protocol 2.
|
|
Experimental Protocol 2: AT1 Receptor Blockade and Acetazolamide. This protocol consisted of three periods (i.e., baseline, acetazolamide, and angiotensin II) in one group of rats that received ARB for 1 week and another group of age-matched control rats. At baseline, control and ARB-treated rats had similar RBF; however, MABP was significantly (p < 0.05) reduced in ARB-treated rats (101 ± 3 mm Hg) compared with control rats (110 ± 3 mm Hg). AZ induced a significant decrease of RBF in both the control rats and in rats treated for 1 week with the ARB, and the magnitude of the AZ-induced RBF decrease was similar in both groups (Fig. 5). The ARB treatment seemed to provide adequate blockade of AT1 angiotensin receptors since intravenous infusion of ANGII (15 ng/min) in period 3 of the study produced a significant reduction of RBF from the previous period in control but not in ARB-treated rats. In addition, ANGII infusion raised MABP in control but not in the ARB-treated rats (Fig. 5).
|
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
A1AR Blockade Alone Increased UV and UNaV without Significantly Altering UKV or RBF. The lack of a kaliuretic effect is in agreement with published data (Knight et al., 1993; Kuan et al., 1993). Natriuretic responses to A1AR antagonists were previously shown to be accompanied by increased fractional excretion of lithium (Knight et al., 1993) and decreased fluid reabsorption in the PT (Wilcox et al., 1999). It also seems likely that some portion of the natriuretic effect of A1AR antagonists occurs secondary to blockade of sodium reabsorption in the collecting duct system (Ma and Ling, 1996; Macala and Hayslett, 2002), where sodium reabsorption normally drives potassium secretion. Interactions at both early and late tubular segments may account for the balanced effects of A1AR blockade on renal potassium handling observed in this and other studies. Also consistent with published data, we did not observe a decrease of RBF associated with the natriuretic effect of A1AR blockade. Given their diuretic effect in the PT, one might expect these agents to trigger TGF producing a decrease of RBF. However, adenosine is believed to be the chemical mediator of TGF, and murine gene knockout models that lack A1AR do not exhibit intact TGF responses (Brown et al., 2001; Sun et al., 2001). Likewise, pharmacological blockade of A1AR in the afferent arteriole seemed to inhibit TGF-mediated reductions of RBF despite increased delivery of NaCl out of the PT induced by A1AR blockade in this tubular region.
A1AR Blockade Attenuated the UKV Induced by Acetazolamide. It was previously reported that A1AR blockade had additive natriuretic effects with furosemide and that the combination did not induce UKV beyond that of furosemide alone (Gellai et al., 1998). Our results are similar in that we also found an additive natriuretic response with the combination of DPCPX and AZ. When compared with AZ alone, the combination produced a lesser kaliuretic response, indicating that A1AR blockade blunted the UKV associated with AZ treatment despite augmented sodium output. Collectively, these data indicate that A1AR antagonists may enhance UNaV and attenuate UKV when used in combination with other diuretic agents.
A1AR Blockade Did Not Blunt the Decrease of RBF Induced by Acetazolamide. Studies using murine gene deletion models (i.e., sodium-hydrogen exchanger 3-/- and aquaporin 1-/-) have demonstrated that reduced proximal sodium and water reabsorption results in diminished GFR and RBF relative to wild-type mice (Schnermann et al., 1998; Lorenz et al., 1999). Crossing of the aquaporin 1-/- knockout mouse with an A1AR-/- knockout mouse produced a model with reduced proximal fluid reabsorption but absent TGF responses (Hashimoto et al., 2004b). Despite reduced proximal fluid reabsorption, the single nephron GFR was essentially normal in these double knockout mice, indicating that A1AR-linked TGF interactions can lead to a decrease of RBF and GFR in situations where proximal tubular fluid reabsorption is impaired.
In view of the studies described above, we had postulated that AZ-induced inhibition of proximal sodium and fluid reabsorption would initiate a TGF-mediated reduction of RBF through activation of A1AR on afferent arterioles in un-treated rats and that A1AR blockade would abolish the response in DPCPX-treated rats. Our observation that pharmacological A1AR blockade with DPCPX did not attenuate the AZ-induced RBF decrease was unexpected. One possible explanation is that the infusion rate of DPCPX used in our study may have been inadequate to block A1AR. However, we observed a significant diuretic/natriuretic response to the infused DPCPX and an attenuation of AZ-induced kaliuresis. In addition, heart rate tended to be elevated in the DPCPX-treated rats indicative of systemic A1AR blockade.
Another possible explanation for the inability of DPCPX to block AZ-induced renal hemodynamic changes is that the adenosine A1AR interaction may not mediate TGF. Indeed, there is controversy regarding the identity of the TGF mediator, with some data suggesting that ATP may play a prominent role (Nishiyama and Navar, 2002). For example, macula densa cells released ATP during perturbations of luminal NaCl concentrations (Bell et al., 2003), and renal interstitial ATP levels increased, whereas levels of adenosine did not change, in response to AZ-induced natriuresis (Nishiyama et al., 2000). After release from macula densa, ATP may directly activate purinergic receptors to induce afferent arteriolar vasoconstriction. However, there are data indicating that ATP undergoes conversion to adenosine via the catalytic activity of nucleotidases, and the resulting adenosine activates TGF through A1AR stimulation (Thomson et al., 2000; Castrop et al., 2004).
An additional explanation for our observation is that the renal hemodynamic response to CAI may occur independent of the TGF mechanism. An earlier study demonstrated that the CAI benzolamide induced a similar magnitude decrease of GFR and RBF in both A1AR-/- knockout and wild-type mice, despite the absence of TGF responses in the A1AR-/- knockout mice (Hashimoto et al., 2004a). Our data, using pharmacological blockade of A1AR, are consistent with these findings. Interestingly, Hashimoto et al. (2004a) also found that acute AT1 angiotensin receptor blockade significantly attenuated renal hemodynamic responses to benzolamide in both groups of mice, indicating that activation of the RAS may be responsible for the CAI-induced RBF response.
Angiotensin AT1 Receptor Blockade Did Not Prevent the Acetazolamide-Induced Renal Hemodynamic Response in Rats. Based on the work by Hashimoto et al. (2004a) described above, we designed an experiment in which we treated rats with the ARB L158809 for 1 week and examined the response to AZ. Contrary to our expectation, we found that the decrease of RBF in response to AZ was not attenuated by ARB treatment. To verify blockade of AT1 angiotensin receptors, the rats were infused with ANGII during the final period of the study. We found that ANGII caused a significant reduction of RBF and increase of MABP in control but not in ARB-treated rats. In addition, baseline MABP was reduced in ARB-treated rats. Collectively, our data indicate that vascular AT1 receptors were indeed blocked by ARB treatment, but this did not diminish the renal hemodynamic response to AZ.
Our renal hemodynamic data in rats obviously differ from that of Hashimoto et al. (2004a) in mice. However, our results are in general agreement with Deng et al. (2002), who reported that in the rat, angiotensin-converting enzyme inhibitor treatment did not block the RBF decrease induced by benzolamide. Interestingly, plasma and kidney ANGII concentrations in the rats were not significantly increased after benzolamide infusion (Deng et al., 2004), whereas Hashimoto et al. (2004a) found that plasma renin concentrations were elevated in mice after CAI. These data indicate that the RAS may play a greater role in mediating the renal hemodynamic effects of CAI in mice compared with rats. Of note, there are recognized species differences regarding the contribution of the RAS to maintenance of blood pressure (Cholewa et al., 2005), with mice having elevated plasma renin concentrations relative to other species. Furthermore, blood pressure seems to be more dependent upon the endogenous RAS and thus more sensitive to RAS inhibition in mice compared with rats. The clinical implications of the species differences noted here and in other studies are difficult to predict given that RAS function is qualitatively similar in mice and rats despite quantitative differences in individual components of the system.
Our experiments provide evidence that neither adenosine acting at A1AR nor ANGII acting at AT1 receptors mediates the acute decrease of RBF following CAI in the rat. A limitation of our study is that we did not assess GFR and cannot directly address the role of A1AR, AT1 receptors, or TGF in mediating CAI-induced changes of GFR. It has been suggested that the GFR decrease following CAI may be explained by an increase of hydrostatic pressure in the tubules due to enhanced fluid delivery to distal segments, resulting in decreased net filtration pressure in the glomeruli (Leyssac et al., 1994). Although this may account for reported alterations in GFR, it seems unlikely to explain the decrease of RBF. Further work is needed to identify the mechanism(s) responsible for renal hemodynamic changes following CAI in the rat.
In summary, A1AR blockade alone produced diuresis and natriuresis without significant perturbations of UKV or RBF. When combined with a CAI, A1AR blockade had additive effects on UNaV and attenuated the AZ-induced UKV. These data indicate that A1AR antagonists are likely to inhibit sodium reabsorption in multiple sites along the tubule and may be useful diuretic agents alone or in combination with other conventional diuretic agents. The decrease of RBF that occurred in response to CAI was not inhibited by A1AR blockade and did not seem to be mediated by a TGF/A1AR-dependent mechanism. In the mouse, the response may be mediated through the RAS; however, our data and that of others indicate that the renal hemodynamic response to CAI in the rat occurs independent of the RAS.
|
Footnotes |
|---|
A portion of this work was presented as a poster at the 2004 Renal Week Conference of the American Society of Nephrology; 2004 October 27-November 1; St. Louis, MO.
ABBREVIATIONS: GFR, glomerular filtration rate; RBF, renal blood flow; CAI, carbonic anhydrase inhibitor; PT, proximal tubule; TGF, tubuloglomerular feedback; A1AR, A1 adenosine receptor; MABP, mean arterial blood pressure; DPCPX, 1,3-dipropyl-8-cyclopentylxanthine (DP); DMSO, dimethylsulfoxide; Vh, vehicle; AZ, acetazolamide; AT1 receptor, angiotensin II type 1 receptor; ANGII, angiotensin II; ARB, angiotensin AT1 receptor blocker; L158809, 5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5yl)[1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine; UV, urine excretion rate; UNaV, urinary excretion rate of sodium; UKV, urinary excretion rate of potassium; ANOVA, analysis of variance; RAS, reninangiotensin system.
Address correspondence to: Curtis K. Kost, Jr., Department of Basic Biomedical Sciences, University of South Dakota School of Medicine, 218 Lee Medical Bldg, 414 East Clark Street, Vermillion, SD 57069. E-mail: ckost{at}usd.edu
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Bell PD, Lapointe JY, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K, Kovacs G, and Okada Y (2003) Macula densa cell signaling involves ATP release through a maxi anion channel. Proc Natl Acad Sci USA 100: 4322-4327.
Brater DC (1998) Diuretic therapy. N Engl J Med 339: 387-395.
Brown R, Ollerstam A, Johansson B, Skott O, Gebre-Medhin S, Fredholm B, and Persson AE (2001) Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice. Am J Physiol 281: R1362-R1367.
Castrop H, Huang Y, Hashimoto S, Mizel D, Hansen P, Theilig F, Bachmann S, Deng C, Briggs J, and Schnermann J (2004) Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice. J Clin Investig 114: 634-642.[CrossRef][Medline]
Chang RS, Siegl PK, Clineschmidt BV, Mantlo NB, Chakravarty PK, Greenlee WJ, Patchett AA, and Lotti VJ (1992) In vitro pharmacology of L-158,809, a new highly potent and selective angiotensin II receptor antagonist. J Pharmacol Exp Ther 262: 133-138.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, et al. (2003) Seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Hypertension 42: 1206-1252.
Cholewa BC, Meister CJ, and Mattson DL (2005) Importance of the reninangiotensin system in the regulation of arterial blood pressure in conscious mice and rats. Acta Physiol Scand 183: 309-320.[CrossRef][Medline]
Deng A, Hammes JS, and Thomson SC (2002) Hemodynamics of early tubuloglomerular feedback resetting during reduced proximal reabsorption. Kidney Int 62: 2136-2143.[CrossRef][Medline]
Deng A, Wead LM, and Blantz RC (2004) Temporal adaptation of tubuloglomerular feedback: effects of COX-2. Kidney Int 66: 2348-2353.[CrossRef][Medline]
Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, and Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53: 527-552.
Gellai M, Schreiner GF, Ruffolo RR Jr, Fletcher T, DeWolf R, and Brooks DP (1998) CVT-124, a novel adenosine A1 receptor antagonist with unique diuretic activity. J Pharmacol Exp Ther 286: 1191-1196.
Gottlieb SS, Brater DC, Thomas I, Havranek E, Bourge R, Goldman S, Dyer F, Gomez M, Bennett D, Ticho B, et al. (2002) BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 105: 1348-1353.
Hashimoto S, Huang YG, Castrop H, Hansen PB, Mizel D, Briggs J, and Schnermann J (2004a) Effect of carbonic anhydrase inhibition on GFR and renal hemodynamics in adenosine-1 receptor-deficient mice. Pflueg Arch Eur J Physiol 448: 621-628.[CrossRef][Medline]
Hashimoto S, Huang Y, Mizel D, Briggs J, and Schnermann J (2004b) Compensation of proximal tubule malabsorption in AQP1-deficient mice without TGF-mediated reduction of GFR. Acta Physiol Scand 181: 455-462.[CrossRef][Medline]
Hawkins RG and Houston MC (2005) Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the United States? A hypothesis. Am J Hypertens 18: 744-749.[CrossRef][Medline]
Jackson EK, Kost CK Jr, Herzer WA, Smits GJ, and Tofovic SP (2001) A(1) receptor blockade induces natriuresis with a favorable renal hemodynamic profile in SHHF/Mcc-fa(cp) rats chronically treated with salt and furosemide. J Pharmacol Exp Ther 299: 978-987.
Kim GH (2004) Long-term adaptation of renal ion transporters to chronic diuretic treatment. Am J Nephrol 24: 595-605.[CrossRef][Medline]
Knight RJ, Bowmer CJ, and Yates MS (1993) The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist. Br J Pharmacol 109: 271-277.[Medline]
Kost CK Jr, Herzer WA, Rominski BR, Mi Z, and Jackson EK (2000) Diuretic response to adenosine A(1) receptor blockade in normotensive and spontaneously hypertensive rats: role of pertussis toxin-sensitive G-proteins. J Pharmacol Exp Ther 292: 752-760.
Kramer BK, Schweda F, and Riegger GA (1999) Diuretic treatment and diuretic resistance in heart failure. Am J Med 106: 90-96.[CrossRef][Medline]
Kuan CJ, Herzer WA, and Jackson EK (1993) Cardiovascular and renal effects of blocking A1 adenosine receptors. J Cardiovasc Pharmacol 21: 822-828.[Medline]
Leyssac PP, Karlsen FM, Holstein-Rathlou NH, and Skott O (1994) On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption. Am J Physiol 266: R1544-R1550.[Medline]
Lorenz JN, Schultheis PJ, Traynor T, Shull GE, and Schnermann J (1999) Micropuncture analysis of single-nephron function in NHE3-deficient mice. Am J Physiol 277: F447-F453.[Medline]
Macala LJ and Hayslett JP (2002) Basolateral and apical A1 adenosine receptors mediate sodium transport in cultured renal epithelial (A6) cells. Am J Physiol 283: F1216-F1225.
Ma H and Ling BN (1996) Luminal adenosine receptors regulate amiloride-sensitive Na+ channels in A6 distal nephron cells. Am J Physiol 270: F798-F805.[Medline]
Na KY, Oh YK, Han JS, Joo KW, Lee JS, Earm JH, Knepper MA, and Kim GH (2003) Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats. Am J Physiol 284: F133-F143.
Nishiyama A, Majid DS, Taher KA, Miyatake A, and Navar LG (2000) Relation between renal interstitial ATP concentrations and autoregulation-mediated changes in renal vascular resistance. Circ Res 86: 656-662.
Nishiyama A and Navar LG (2002) ATP mediates tubuloglomerular feedback. Am J Physiol 283: R273-R275; discussion R278-R279.
Nomura H, Nagashima K, Kusaka H, and Karasawa A (1995) Antihypertensive effects of KW-3902, an adenosine A1-receptor antagonist, in Dahl salt-sensitive rats. Jpn J Pharmacol 68: 389-396.[Medline]
Osswald H, Hermes HH, and Nabakowski G (1982) Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int Suppl 12: S136-S142.[Medline]
Schnermann J, Chou CL, Ma T, Traynor T, Knepper MA, and Verkman AS (1998) Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice. Proc Natl Acad Sci USA 95: 9660-9664.
Siegl PK, Chang RS, Mantlo NB, Chakravarty PK, Ondeyka DL, Greenlee WJ, Patchett AA, Sweet CS, and Lotti VJ (1992) In vivo pharmacology of L-158,809, a new highly potent and selective nonpeptide angiotensin II receptor antagonist. J Pharmacol Exp Ther 262: 139-144.
Sun D, Samuelson LC, Yang T, Huang Y, Paliege A, Saunders T, Briggs J, and Schnermann J (2001) Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci USA 98: 9983-9988.
Thomson S, Bao D, Deng A, and Vallon V (2000) Adenosine formed by 5'-nucleotidase mediates tubuloglomerular feedback. J Clin Investig 106: 289-298.[Medline]
Tucker BJ, Steiner RW, Gushwa LC, and Blantz RC (1978) Studies on the tubuloglomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide. J Clin Investig 62: 993-1004.[Medline]
Uehara Y, Numabe A, Hirawa N, Kawabata Y, Nagoshi H, Kaneko H, Gomi T, Goto A, Toyo-oka T, and Omata M (1995) A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats. Am J Hypertens 8: 1189-1199.[CrossRef][Medline]
van Buren M, Bijlsma JA, Boer P, van Rijn HJ, and Koomans HA (1993) Natriuretic and hypotensive effect of adenosine-1 blockade in essential hypertension. Hypertension 22: 728-734.
Welch WJ (2002) Adenosine A1 receptor antagonists in the kidney: effects in fluid-retaining disorders. Curr Opin Pharmacol 2: 165-170.[CrossRef][Medline]
Wilcox CS, Welch WJ, Schreiner GF, and Belardinelli L (1999) Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist. J Am Soc Nephrol 10: 714-720.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|
 |
 |
 |
