Angiotensin I-forming angiotensinogenases in extrarenal vasculature and in the kidney.

The intention of this study was to characterize angiotensin I-forming angiotensinogenases (AIFAs) in rat extrarenal arterial walls and to clarify whether these enzymes are also present in the kidney. A further aim was to identify AIFAs in human vasculature and to establish whether they are affected in essential hypertension. Sprague-Dawley rats and vascular sections of patients undergoing corrective surgery were studied. Enzyme kinetic assays were performed using angiotensin I radioimmunoassay and purified natural angiotensinogens. Fast protein liquid chromatography was employed for biochemical characterization. A series of AIFAs with various isoelectric points, molecular weights and pH optima was detected in rat extrarenal vascular and, with differing distributions of enzyme activities, in renal tissues. In extrarenal arteries the main form of renal renin was present with a relatively low activity only. AIFAs were also demonstrable in human extrarenal vasculature and behaved like plasma renin in essential hypertension. The results indicate the existence of an intrinsic human vascular RAS in extrarenal (and renal) arteries. Extrarenal arterial AIFAs are not generally stimulated in essential hypertensives, as previously postulated.

Reninlike enzymes in human vasculature.

The present study was designed to identify angiotensin I (Ang I)-forming angiotensinogenases in human extrarenal vasculature and to examine the theory of Jiménez Días on their stimulation in essential hypertension. Vascular sections obtained intraoperatively from 14 normotensive and 16 hypertensive patients undergoing corrective surgery, 68 umbilical cord blood vessels from parturient women, tissue samples from nine explanted hearts, and serum from anephric and healthy individuals were investigated. Ang I-forming angiotensinogenase activities were determined enzyme-kinetically by using Ang I radioimmunoassay and purified sheep or human angiotensinogens. Three nonrenin Ang I-forming angiotensinogenases (pH optima of 4.0, 5.1, and 6.1) were identified in extrarenal vasculature, in cardiac tissues, and in plasma. Highest specific activities of nonrenin Ang I-forming angiotensinogenase (in nanograms Ang I per gram times hour; mean +/- SD) were found in cardiac tissue (2,821 +/- 497, n = 9), followed by carotid artery intima (1,448 +/- 982, n = 10), arteries (1,307 +/- 736, n = 18), and umbilical cord arteries (135 +/- 55, n = 35). Extrarenal arterial Ang I-forming angiotensinogenases were linearly correlated with those of local angiotensin converting enzyme and plasma renin activity. In essential hypertension, extrarenal arterial Ang I-forming angiotensinogenases were scattered, but not generally stimulated. The data obtained indicate the existence of nonrenin Ang I-forming angiotensinogenases in human extrarenal vasculature, in kidney, and in plasma. The postulate of stimulation of extrarenal arterial Ang I-forming angiotensinogenases in essential hypertension cannot be supported. Similar to the classification of plasma renin activity, a classification of Ang I-forming angiotensinogenase activity is proposed, consisting of patients with essential hypertension divided into subgroups exhibiting high, normal, or low vascular Ang I-forming angiotensinogenase activities.

Suppression of renin-angiotensin system in the heart of spontaneously hypertensive rats.

Renin-like enzyme and angiotensin converting enzyme (ACE) were identified and their specific activities measured in cardiac tissues of spontaneously hypertensive rats (SHR) and their Wistar-Kyoto (WKY) normotensive controls. In addition, the enzyme activities were determined following administration of hypotensive drugs. The pH optima of cardiac renin-like enzymes were identical with those in vascular walls, the specific activity being higher in the heart. Cardiac ACE revealed similarities with the venous wall enzyme. The highest specific cardiac renin-like activity was found in the septum and that of ACE in atria/auricles. Both enzyme values were lower in the hearts of SHR than in those of normotensive controls. Following nifedipine treatment, specific renin-like activities increased in all cardiac structures studied (P less than 0.01); with nitrendipine and muzolimine less pronounced elevations were obtained. Administration of these three hypotensive drugs resulted in a stimulation of ACE in all the cardiac structures except in atria/auricles, where their activities were lowered.

Effect of hypotensive agents on the renin-angiotensin system in vascular walls of spontaneously hypertensive rats.

Previous investigations have shown that the renin-angiotensin system (RAS) is activated in vascular walls of spontaneously hypertensive rats (SHR). The present study was undertaken to determine whether antihypertensive drugs attenuate this activation. Two calcium channel blockers, nifedipine and nitrendipine, and the diuretic muzolimine were applied to SHR for 2-4 weeks, and angiotensin (ANG) I-forming angiotensinogenase (AIFA) and ANG I converting enzyme (ACE) activities were determined. The values for both enzymes were elevated in arterial tissues of SHR (P less than 0.01), whereas in venous walls AIFA activity was decreased (P less than 0.01). All hypotensive drugs reduced arterial ACE activities in SHR (nifedipine and muzolimine: P less than 0.01; nitrendipine: P less than 0.05). Angiotensin I-forming angiotensinogenase activity was increased following treatment with nifedipine (P less than 0.01) but reduced by nitrendipine (P less than 0.05); with muzolimine, no significant alterations were observed. The results obtained indicate that in SHR, stimulation of vascular wall ACE is abolished following treatment with hypotensive agents, and the effect is independent of their mode of action. It is assumed that the activation of vascular ACE is not caused by, but rather a reaction to, elevated blood pressure.