Investigations of components of the renin-angiotensin system in rat vascular tissue.

Abstract

SUMMARY Investigations were performed on components of the renin-angiotensin system (RAS) in homogenate extracts of vascular tissue and aortic smooth muscle cells cultivated in vitro. Determinations of isoelectric points and pH optima indicated the existence in aortic homogenate extracts of two local angiotensin I (AI)-forming enzymes (AIFE) that were different from those of plasma, renal cortex, veins, and aortic smooth muscle cells. The pH optima for Al-converting enzyme (ACE) from vascular tissues, aortic smooth muscle cells, and plasma were in the same range (pH 8.0-8.5), and in agreement with those measured previously in other tissues. In contrast, in vitro studies with the ACE inhibitors MK-421 and MK-422 and measurement of isoelectric points suggested that aortic ACE was different from the plasma enzyme. AIFE and ACE activities were found to be elevated in spontaneously hypertensive rats (SHR). The biochemical characteristics of the enzymes investigated in the vascular tissue of SHR were not different from those of the normotensive controls. AI-and All-degrading enzymes were found both in aortic tissue and in aortic smooth muscle cells. One potent Al-degrading enzyme different from ACE was observed in aortic tissue. A high ratio of AI/AII immunoreactivities in arterial walls suggests the availability of renin substrate, and that Al-degrading enzymes are the rate-limiting enzymes for AH formation. were the first to demonstrate the existence of arterial and also venous wall renin by using systematically performed biochemical methods. In the last few years, there has been renewed interest in the vascular reninangiotensin system (RAS). Now, as before, it is thought to play a role in the regulation of blood pressure and in the development and maintenance of hypertension. The present investigation continues our previous studies in this field 4 ' 3 and was undertaken to recognize, quantify, and partly characterize those components of

Beta-adrenergic-induced local angiotensin generation in the rabbit hind limb is dependent on the kidney.

“…1 -3 In vitro studies have demonstrated the existence of renin, angiotensinogen mRNA, angiotensinogen, angiotensin converting enzyme, angiotensin I (Ang I) and angiotensin II (Ang II) in the vascular wall. 4 -7 Ang I or Ang II is generated in and released from in vitro preparations of rat mesenteric arteries, 8 rat kidney, 910 and rat hind legs 1112 and in vivo from canine kidney 13 and rabbit renal and femoral vascular beds.…”

Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries.

“…This indicates that the converting enzyme is operative in mesenteric resistance arteries of SHR and is interconnected with the vascular production of endothelin. 32 The fact that the potentiation was observed only in SHR suggests a pathophysiological role of endogenous endothelin in hypertension. As judged from the circulating levels of endothelin-1, 10 -13 the vascular production of the peptide is low.…”

Reninlike enzymes in human vasculature.

“…Ang I-forming angiotensinogenase activities were measured enzyme-kinetically by using the Ang I radioimmunoassay 3 and sheep or, in some cases, human angiotensinogen. Renin substrates were prepared as described previously.…”

“…2 Furthermore, it has been found that extrarenal arterial wall Ang I-forming angiotensinogenases, biochemically different from renal renin, are stimulated in spontaneously hypertensive rats. 3 - 4 Recently, we noticed in the rat that those nonrenin Ang I-forming angiotensinogenases identified in extrarenal arteries are also contained in the kidney, although renal renin was scarcely demonstrable in extrarenal vasculature (authors' unpublished observations).…”