Angiotensins in plasma of hypertensive rats and human
Introduction
In the angiotensin metabolic cascade, angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE). Recent studies have shown that angiotensin I is also an immediate precursor of two other biologically active angiotensins, namely angiotensin-(1–7) [1], [2] and des-aspartate-angiotensin I (DAA-I) [3], [4]. As a biological active peptide, the plasma level of angiotensin-(1–7) has been shown to vary and reflect the physiological and pathological status of the animal [5], [6]. For DAA-I, the enzyme that specifically converts angiotensin I to DAA-I has been reported to be significantly higher in the plasma of the spontaneously hypertensive rat [7]. In an attempt to know more about the roles of DAA-I in hypertension, the present study investigated the plasma profile of DAA-I in three rat models of hypertension and human essential hypertension, and the effect of angiotensin converting enzyme inhibition on the profile in the SHR and human hypertensive subjects by the technique of capillary electrophoresis. The findings of the present study support earlier suggestions that DAA-I is a physiological peptide involved in the pathophysiology of the cardiovascular system [8], [9], [10].
Section snippets
Animals
The animals used were 3–4 months old male rats (body weight between 270 and 310 g) of the following strains: Sprague–Dawley (SD), left renal artery stenosed hypertensive SD (LRAS), deoxycorticosterone acetate/sodium chloride-induced hypertensive SD (DOCA-salt), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR). The SD rats were supplied by the local University Animal Centre and the WKY and SHR were purchased from the Animal Resource Centre, Western Australia. The mean arterial pressure
Results
Table 2 shows the level of plasma angiotensins in the normo- and hypertensive rats and human. The values were consistent and indicate the advantages of simplicity and accuracy of capillary electrophoresis [7] over the more cumbersome HPLC cum antibody detection of plasma angiotensins where either incomplete HPLC separation of angiotensins or cross-reactivity of antibody with more than one angiotensins were experienced [13], [14], [15]. The plasma concentration of angiotensin II in the SD and
Discussion
The significantly lower level of plasma angiotensin I in the DOCA-salt rat seems to reflect the low level of plasma renin reported for this model of hypertensive rat [17], which could also have resulted in lower but not significant level of plasma angiotensin II and angiotensin III. On the contrary, the plasma level of angiotensin I, angiotensin II and angiotensin III in the LRAS was significantly higher than in the SD. The LRAS is a hypertension model with an initial high plasma renin activity
Acknowledgements
This study was supported by Grant R-184-000-021-213 from the National Medical Research Council, Singapore.
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Cited by (28)
Des-aspartate-angiotensin I, a novel angiotensin AT<inf>1</inf> receptor drug
2015, European Journal of PharmacologyCitation Excerpt :This is equivalent to a daily dose of 12 pmol in a 350 g rat, which is a remarkably low dose. The following calculation shows this dose in terms of total circulating DAA-I. Taking the blood volume of a 350 g rat as 21.77 ml (Lee and Blaufox, 1985), and the circulating plasma concentration of DAA-I as 72 pmolar (Sim and Qui, 2003), the total amount of circulating DAA-I approximates 1.57 pmol. The daily amount of DAA-I administered (12 pmol) was only 7.6 times the total circulating DAA-I.
Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress
2015, Vascular PharmacologyCitation Excerpt :The activity of aminopeptidase X, the enzyme which degrades angiotensin I to DAA-I, is higher in both the endothelium and the plasma of the SHR than in the WKY [52]. However, the plasma DAA-I level is lower in the hypertensive strain as in essential hypertensive patients [53]. This may result from increased activity of angiotensin converting enzyme (ACE) which not only converts angiotensin I into angiotensin II but also DAA-I into angiotensin III [54].
Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide-treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric exercise
2013, Regulatory PeptidesCitation Excerpt :Maximum attenuation was observed at 10− 10 M DAA-I, and significant attenuation was seen with concentration as low as 10− 16 M (Fig. 2). The action of DAA-I at such low concentrations was also seen in earlier in vitro studies [26,27], and could be due to the possibility that circulating DAA-I (present in pmolar range; [28]) was active physiologically. The tissue level of active DAA-I could be much lower than the circulating level.
Fast, selective, and sensitive analysis of low-abundance peptides in human plasma by electromembrane extraction
2012, Analytica Chimica ActaCitation Excerpt :A few years ago, an off-line procedure based on solid-phase microextraction (SPME) coupled to LC–MS (SPME-LC-ESI-MS) was proposed for the direct extraction of the vasoactive peptides angiotensin 1, and angiotensin 2 from whole blood and serum [28]. Both peptides play a central role in the cardiovascular homeostasis [29,30], and the extraction procedure was developed in an attempt to reduce analysis time, sample preparation and cost. After 1 h of extraction, endogenous concentrations of angiotensin peptides in human whole blood were determined.
Rapid isolation of angiotensin peptides from plasma by electromembrane extraction
2009, Journal of Chromatography ABioluminescence immunoassay for angiotensin II using aequorin as a label
2007, Analytical Biochemistry
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Present address: Shanghai Rui-jin Hospital and Shanghai Institute of Hypertension, Shanghai Second Medical University, Shanghai, China.