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The salt intake of an organism controls the number of renin-producing cells in the kidney by yet undefined mechanisms. This study aimed to assess a possible mediator role of preglomerular blood pressure in the control of renin expression by oral salt intake. We used wild-type (WT) mice and mice lacking angiotensin II type 1a receptors (AT1a−/−) displaying an enhanced salt sensitivity to renin expression. In WT kidneys, we found renin-expressing cells at the ends of all afferent arterioles. A low-salt diet (0.02%) led to a moderate twofold increase in renin-expressing cells along afferent arterioles. In AT1a−/− mice, lowering of salt content led to a 12-fold increase in renin expression. Here, the renin-expressing cells were distributed along the preglomerular vascular tree in a typical distal-to-proximal distribution gradient which was most prominent at high salt intake and was obliterated at low salt intake by the appearance of renin-expressing cells in proximal parts of the preglomerular vasculature. While lowering of salt intake produced only a small drop in blood pressure in WT mice, the marked reduction of systolic blood pressure in AT1a−/− mice was accompanied by the disappearance of the distribution gradient from afferent arterioles to arcuate arteries. Unilateral renal artery stenosis in AT1a−/− mice on a normal salt intake produced a similar distribution pattern of renin-expressing cells as did low salt intake. Conversely, increasing blood pressure by administration of the NOS inhibitor N-nitro-l-arginine methyl ester or of the adrenergic agonist phenylephrine in AT1a−/− mice kept on low salt intake produced a similar distribution pattern of renin-producing cells as did normal salt intake alone. These findings suggest that changes in preglomerular blood pressure may be an important mediator of the influence of salt intake on the number and distribution of renin-producing cells in the kidney.

Chronic challenge of renin–angiotensin causes recruitment of renin-producing cells in the kidney along the media layer of afferent arterioles and hypertrophy of cells in the juxtaglomerular apparatus. This study aimed to define the role of nitric oxide (NO) with regard to the recruitment pattern of renin-producing cells and to the possible pathways along which NO could act. We considered the hypothesis that endothelium-derived NO acts via NO-sensitive guanylate cyclase. Mice were treated with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks, which led to a 13-fold increase in renin expression associated with marked recruitment of renin cells in afferent arterioles and hypertrophy of the juxtaglomerular apparatus in wild-type mice. In wild-type mice additionally treated with the nonselective NO synthase inhibitor L-NAME, the recruitment of renin-expressing cells along the afferent arterioles was absent and juxtaglomerular hypertrophy was diminished. An almost identical attenuation of renin cell recruitment as with L-NAME treatment in wild-type mice was found in mice lacking the endothelial isoform of NO synthase. Treatment of mice lacking NO-sensitive guanylate cyclase in renin-expressing cells and preglomerular smooth muscle cells with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks produced juxtaglomerular hypertrophy like in wild-type mice, but no recruitment in afferent arterioles. These findings suggest that endothelium-derived NO and concomitant formation of cGMP in preglomerular renin cell precursors supports recruitment of renin-expressing cells along preglomerular vessels, but not in the juxtaglomerular apparatus.