The aim of this study was to determine the role of renal innervation in the prolonged stimulation of renin secretion and renin synthesis accompanying renal artery stenosis. Male Sprague-Dawley rats, in which the left kidney had been denervated or sham denervated 4 days earlier, received a left renal artery clip (ID 0.2 mm). Plasma renin activity and renin mRNA were assayed 1, 2, or 4 days after...

The physiological role of prorenin is unknown; however, the possibility that prorenin inhibits renin locally has been suggested. We tested the hypothesis that prorenin may be an endogenous competitor for renin uptake in the tissue. We also investigated whether prorenin can be activated to active renin and affect mean arterial pressure (MAP). Isolated perfused hindquarters of rats transgenic for...

To investigate mechanisms involved in the high incidence of hypertension in diabetes mellitus, the relationship between renin-angiotensin production and renal prostaglandin E2 synthesis was studied in rats 1 week after diabetes mellitus had been induced by streptozotocin injection. The diabetic rats became hypertensive, although plasma renin activity did not increase despite the plasma volume c...

Gap junctional coupling of renin-producing cells is of major functional importance for the control of renin synthesis and release. This study was designed to determine the relevance of the vascular gap junction protein connexin 45 (Cx45) for the control of renin expression and secretion. By crossbreeding mice which drive Cre recombinase under the control of the endogenous renin promoter with mi...

In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic reni...

Our previous studies support the hypothesis that activation of the renin-angiotensin system by renal ischemia elevates adenosine levels and that adenosine acts in a negative feedback loop to limit renin release and to mitigate some of the hypertension-producing effects of angiotensin II. To further test this hypothesis, we compared the time course of caffeine-induced increases in plasma renin a...

In contrast to the negative feedback of angiotensin II (ANG II) on juxtaglomerular renin, ANG II stimulates renin in the principal cells of the collecting duct (CD) in rats and mice via ANG II type 1 (AT1R) receptor, independently of blood pressure. In vitro data indicate that CD renin is augmented by AT1R activation through protein kinase C (PKC), but the exact mechanisms are unknown. We hypot...

The renin-angiotensin system (RAS) regulates blood pressure and fluid-electrolyte homeostasis. A key step in the RAS cascade is the regulation of renin synthesis and release by the kidney. We and others have shown that a major mechanism to control renin availability is the regulation of the number of cells capable of making renin. The kidney possesses a pool of cells, mainly in its vasculature ...

OBJECTIVE Mannose 6-phosphate receptors (M6PR) bind both renin and prorenin, and such binding contributes to renin/prorenin clearance but not to angiotensin generation. Here, we evaluated the kinetics of renin/prorenin binding to the recently discovered human (pro)renin receptor (h(P)RR), and the idea that such binding underlies tissue angiotensin generation. METHODS AND RESULTS Vascular smoo...

1. A renin-like enzyme in aortic tissue of the spontaneously hypertensive rat was found to be a freely dissociable enzyme (saline homogenization) with an affinity for the renin inhibitor pepstatin. At neutral pH values, the enzyme was active in homologous plasma to produce angiotensin I, and therefore distinct from pseudorenin and cathepsin D. The arterial enzyme and semi-purified renal renin c...