Renin Uptake by the Endothelium Mediates Vascular Angiotensin Formation

Abstract

Abstract-We investigated the role of the vascular endothelium in the local production of angiotensin. Angiotensin release from isolated rat hindquarters perfused with an artificial medium was measured by high-performance liquid chromatography and radioimmunoassay. Perfused hindquarters with endothelium released angiotensin I spontaneously, indicating ongoing renin-angiotensinogen reaction. Endothelium denudation (by a detergent, validated by electron microscopy and by the absence of a vasodilator response to acetylcholine) reduced angiotensin I release by Ͼ90%, whereas bilateral nephrectomy 24 hours before perfusion abolished the release completely. Infusion of renin into perfused hindquarters induced sustained local angiotensin I release in the presence of an intact endothelium but not after endothelium denudation. The conversion of angiotensin I to angiotensin II was abrogated by endothelium denudation, whereas the disappearance of angiotensin II was unchanged. Endothelium denudation diminished the pressor response to angiotensin II but abolished the response to renin and angiotensin I. Expression of renin messenger RNA, investigated by reverse-transcription polymerase chain reaction using 4 different primer combinations, was not detected in up to 5 g vascular RNA, whereas a renin signal was readily detected with 5 ng kidney RNA.

Increased hypothalamic angiotensin-(1–7) levels in rats with aortic coarctation-induced hypertension

“…A possible explanation may be that the increased renal levels of Ang II (present results) may be due to renal uptake of circulating renin, as suggested by Campbell et al in kidneys from transgenic hypertensive rats [2]. In fact, Ang formation mediated by renin uptake has been demonstrated in cardiac and coronary vascular tissues [8,20] and in the endothelium [14]. Our results indicate that conversion of Ang I to Ang II was not changed, that is, the Ang II/Ang I ratio in the CH rat kidney was similar to that of the sham-operated rats.…”

Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats

“…Renin and angiotensinogen may be synthesized locally, or may be taken up from the circulating blood (14). In a recent study, angiotensin generation in rat hindquarter vessels had ceased 24 h after bilateral nephrectomy (10). In other studies, after bilateral nephrectomy, plasma renin declined faster than aortic renin and blood pressure responses to converting enzyme inhibition was better correlated with the aortic renin than with plasma renin concentration (28,29).…”

Renin, Prorenin and the Putative (Pro)renin Receptor

“…A similar concept applies to the vascular wall. 50 Local prorenin synthesis does appear to occur in adrenal, eye, ovaries, and testis. 7,33,51,52 This explains why prorenin is still present in plasma of nephrectomized subjects (Figure 1).…”