Elsevier

Regulatory Peptides

Volume 111, Issues 1–3, 28 March 2003, Pages 179-182
Regulatory Peptides

Angiotensins in plasma of hypertensive rats and human

https://doi.org/10.1016/S0167-0115(02)00289-6Get rights and content

Abstract

The plasma levels of des-aspartate-angiotensin I (DAA-I) in three models of hypertensive rats and hypertensive subjects were determined and compared with their normotensive controls. The rationale for the study was based on our earlier findings showing that DAA-I is a physiological angiotensin peptide that is involved in the pathophysiology of the cardiovascular system. The determination was carried out by the technique of capillary electrophoresis. Plasma level of angiotensin I, angiotensin II, and angiotensin III was also determined as a measurement of the status of the renin–angiotensin system in the different models of hypertension. DAA-I was found to be significantly lower in the spontaneously hypertensive rats (SHR) (46.6±2.5 pmol/l compared to 66.1±3.4 pmol/l for the normotensive control Wistar Kyoto rats), renal hypertensive rats (54.2±5.1 pmol/l compared to 72±2.5 pmol/l for the normotensive control Sprague–Dawley rats), and essential human hypertensive subjects (15.2±0.9 pmol/l compared to 19.5±2.5 pmol/l for the normotensive adult), whilst plasma concentration of angiotensin I and angiotensin II is reflective of the state of the renin–angiotensin system in the particular model of hypertension. When the SHR and human hypertensive subjects were treated with an angiotensin converting enzyme (ACE) inhibitor, the plasma level of DAA-I increased significantly. These findings suggest that the low plasma level of DAA-I could be a characteristic defect of the renin–angiotensin system in the two genetic models of hypertension (SHR and human essential hypertensive subjects). The increase of the nonapeptide following ACE inhibitor treatment could be an important hitherto unrecorded contributory factor to the effectiveness of ACE inhibitors in combating heart pathology.

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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    Present address: Shanghai Rui-jin Hospital and Shanghai Institute of Hypertension, Shanghai Second Medical University, Shanghai, China.

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