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 (AT 1aϪ/Ϫ) 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 reninexpressing cells along afferent arterioles. In AT 1aϪ/Ϫ 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 AT 1aϪ/Ϫ mice was accompanied by the disappearance of the distribution gradient from afferent arterioles to arcuate arteries. Unilateral renal artery stenosis in AT 1aϪ/Ϫ mice on a normal salt intake produced a similar distribution pattern of reninexpressing 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 AT1aϪ/Ϫ 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.
AT1a knockoutTHE MAINTENANCE OF SALT HOMEOSTASIS is a central function of the renin-angiotensin-system. A threat to salt balance leads to compensatory changes in renin expression in the kidney in a way that the number of renin-expressing cells increases during salt deficiency and decreases during salt overload (41). It is assumed that the salt-related changes in renin-expressing cells in the kidney are not caused by cell proliferation or apoptosis, but instead result from reversible phenotype changes of preglomerular smooth muscle cells into renin-producing cells and vice versa (34). The intracellular signaling pathways defining the specific phenotype of these cells are yet unknown. Furthermore, it is unclear by which mechanisms salt balance controls the number of renin-producing cells. It has been suggested that the effects of salt balance may affect renin expression in the preglomerular afferent arterioles by autacoids such as nitric oxide (NO) or prostaglandins (42) since salt intake has been shown to control the juxtaglomerular expression of cyclooxygenase-2 (COX-2) (17) and nitric oxide synthase-1 (NOS-1) (37...