Potassium control of extrarenal renin secretion in transgenic (mRen-2)27 and normal rats

Plasma active renin and prorenin were followed for 12 h after bilateral, unilateral, and sham nephrectomy (BNx, UNx, and SNx) in anesthetized transgenic (mRen-2)27 rats to compare them with Sprague-Dawley and spontaneously hypertensive rats (SDR and SHR). In Ren-2 rats, active renin and prorenin increased with plasma potassium post-BNx and were augmented by potassium infusion. The increase in prorenin but not active renin was abolished by bilateral adrenalectomy (BADRx). However, this did not reduce prorenin below normal, indicating that the high plasma prorenin Ren-2 phenotype is not only of adrenal origin. SNx and UNx also raised plasma active renin and prorenin in Ren-2 rats, with positive correlations to plasma potassium. In SDR and SHR, active renin fell below prorenin post-BNx, and adrenal ablation and potassium loading (in SDR) modified the decreasing active renin profile consistent with low levels of regulated extrarenal secretion. In Ren-2 rats, adrenal but not extra-adrenal prorenin secretion is potassium sensitive and stress related. The unidentified source of active renin in BNx+BADRx Ren-2 rats is also potassium and stress related.

Ontogenetic regulation of mouse Ren-2d renin gene in transgenic hypertensive rats, TGR(mREN2)27

TGR(mREN2)27 is a new monogenetic rat model with fulminant hypertension, low kidney renin, and high extrarenal renin gene expression. This study characterizes and compares expression of the Ren-2 gene in TGR(mREN2)27 with that in DBA/2 mice and with renin gene expression in rats. Except in the submandibular gland, the tissue-specific expression of Ren-2 is similar in TGR(mREN2)27 and DBA/2. This demonstrates maintenance of tissue specificity. Organs that are involved in cardiovascular regulation, such as the adrenal gland, kidney, and brain, express the Ren-2 gene before hypertension has developed, consistent with the possibility of a causal relationship between transgene expression in these tissues and hypertension. Because these tissues express the renin gene in nontransgenic rats as well, we suggest that this model can be used to study the regulation of renin gene expression and its role in hypertension at these sites. In addition, as an indication that interactions may exist between blood pressure and renin gene expression, we describe reciprocal changes in blood pressure and Ren-2 mRNA levels in the kidney and brain.

Physiological concentrations of ANP exert a dual regulatory influence on renin release in conscious dogs

The influence of physiological increments in circulating atrial natriuretic peptide (ANP) on renin release was determined in conscious dogs. Renin stimulus-response curves (RSRCs) were obtained by controlled reductions of renal perfusion pressure (RPP) under control conditions and during intrarenal or intravenous ANP infusions. Under all experimental conditions, the RSRCs were characterized by a plateau, a threshold pressure (Pth), and a steep slope below Pth. Intrarenal ANP infusion (0.9 ng.kg-1.min-1), which induced a calculated threefold elevation of renal arterial ANP concentration (but did not change systemic arterial ANP levels), increased the slope of the RSRC by 81% (P less than 0.05) with no effect on Pth. A quantitatively similar effect on the slope of the RSRC (+90%; P less than 0.05) was observed when systemic ANP levels were raised (from 37 +/- 2 to 71 +/- 9 pg/ml; P less than 0.05) by intravenous infusions (3.6 ng.kg-1.min-1). In addition, however, intravenously infused ANP reduced Pth from 91 to 85 mmHg (P less than 0.05), which caused a complete suppression of the renin response to a reduction of RPP down to 85 mmHg. These findings indicate that ANP can inhibit renin release at physiological plasma concentrations by shifting the RSRC to a lower pressure level; this shift is mediated by a modulation of extrarenal renin control mechanisms. The direct effect of ANP on renin release is one of stimulation.