Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation

Background. This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT₁ and cAT₂) in the kidney and adrenal. Methods. Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of dogs: dogs maintained on low-sodium diet for two weeks followed by a high-sodium diet for two weeks (H), and dogs were maintained on the reverse schedule (L). Results. Analysis of the binding data showed that dietary sodium manipulation had no significant effects on cAT₁ and cAT₂ receptor binding affinities in glomeruli, renal medulla, and adrenal tissues. In contrast, dietary sodium loading induced a marked increase in cAT₁ receptor expression in both the glomeruli and adrenal compared with receptor expression in salt-restricted animals [H/L ratio: Glomeruli (1.5), renal medulla (1.1), adrenal (1.6)] that inversely correlated with the activity of the plasma renin angiotensin system. Conversely, adrenal cAT₂ receptor expression was regulated in an inverse manner in the H and L animal groups [H/L ratio: 0.7]. Conclusions. This study demonstrates that renal glomerular and adrenal AT₁ receptors in the dog are coordinately down-regulated by dietary sodium restriction compared with sodium loading, which is distinctly different from the reciprocal regulation observed for rat AT₁ receptors in these tissues. Collectively, these data suggest that postreceptor events in dogs are determinants of the aldosterone response observed during sodium restriction. These findings have important implications for the regulation of the renin-angiotensin system in humans, and suggest that coordinate regulation of AT₁ receptors in the adrenal and glomeruli represent a negative feedback mechanism that when functioning normally prevents fluctuations of arterial blood pressure and development of arterial hypertension in response to changes in dietary sodium.