PT  - JOURNAL ARTICLE
AU  - K A Kirchner
TI  - Role of medullary plasma flow in the attenuated furosemide response in indomethacin-treated rats.
DP  - 1989 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 757--761
VI  - 249
IP  - 3
4099  - http://jpet.aspetjournals.org/content/249/3/757.short
4100  - http://jpet.aspetjournals.org/content/249/3/757.full
SO  - J Pharmacol Exp Ther1989 Jun 01; 249
AB  - To determine the role of medullary hemodynamics in the attenuated furosemide response observed during prostaglandin synthesis inhibition, medullary plasma flow was measured by the albumin accumulation technique in nondiuretic rats and during furosemide administration (4 mg/kg b.wt./hr) in indomethacin- or indomethacin vehicle-treated rats. As in previous studies indomethacin attenuated furosemide chloruresis (FeCl: 11.4 +/- 1.1 vs. 5.0 +/- 0.9%, P less than .001) without altering mean arterial pressure, inulin clearance or total renal blood flow. Medullary plasma flow was not different between nondiuretic rats and furosemide-treated rats (41.4 +/- 4.3 vs. 41.3 +/- 3.4 ml/min/100 g of tissue). Medullary plasma flow was reduced (P less than .05) during indomethacin antagonism of furosemide chloruresis (41.3 +/- 3.4 vs. 29.1 +/- 2.8 ml/min/100 g of tissue). Angiotensin II blockade with saralasin (2 micrograms/kg/min) prevented the fall in medullary plasma flow in indomethacin-treated rats during furosemide infusion but did not alter mean arterial pressure, inulin clearance or total renal blood flow. However, furosemide's chloruretic response in rats treated with both indomethacin and saralasin remained lower (P less than .001) than that in vehicle-treated rats (FeCl 4.7 +/- .94 vs. 11.4 +/- 1.1%) and was not different from that in indomethacin-treated rats. These data demonstrate that although medullary plasma flow is reduced during indomethacin antagonism of furosemide response this change does not contribute to the attenuated chloruresis. Additionally, the dissociation of the antichloruretic and hemodynamic effects of indomethacin observed during saralasin administration suggest that hemodynamic mechanisms are not involved in the attenuated response to furosemide observed during prostaglandin synthesis inhibition.