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The present study was performed to investigate the role of type 1A ANG II (A[T.sub.1A]) receptors in regulating sodium balance and blood pressure maintenance during chronic dietary sodium variations in A[T.sub.1A] receptor-deficient (-/-) mice. Groups of A[T.sub.1A] (-/-) and wild-type mice were placed on a low (LS)-, normal (NS)-, or high-salt (HS) diet for 3 wk. A[T.sub.1A] (-/-) mice on an LS diet had high urinary volume and low blood pressure despite increased renin and aldosterone levels. On an HS diet, (-/-) mice demonstrated significant diuresis, yet blood pressure increased to levels greater than control littermates. There was no effect of dietary sodium intake on systolic blood pressures in wild-type animals. The pressure-natriuresis relationship in A[T.sub.1A] (-/-) mice demonstrated a shift to the left and a decreased slope compared with wild-type littermates. These studies demonstrate that mice lacking the A[T.sub.1A] receptor have blood pressures sensitive to changes in dietary sodium, marked alterations of the pressure-natriuresis relationship, and compensatory mechanisms capable of maintaining normal sodium balance across a wide range of sodium intakes. kidney; pressure-natriuresis relationship; angiotensin II; plasma renin concentration; aldosterone

Research shows that biochemical adenylyl cyclase activity occurs in the basolateral and apical regions of bovine renal epithelial LLC-PK1 cells. Experiments designed to demonstrate the regulatory properties of adenylyl cyclase via Guanine protein-coupled nucleotide binding receptors are described. Immunolocalization and immunofluorescence techniques are used.

Studies the effect of type 1A angiotensin II receptor deletion on blood pressure and sodium excretion during altered dietary salt intake. Effect of dietary sodium content on food intake; Water intake and urinary volume during manipulation of sodium intake; Concentration of serum sodium and potassium; Relationship between blood pressure and natriuresis.

Angiotensin II type 1 (AT1) receptor and D1 and D3 dopamine receptors directly interact in renal proximal tubule (RPT) cells from normotensive Wistar-Kyoto rats (WKY). There is indirect evidence for a D5 and AT1 receptor interaction in WKY and spontaneously hypertensive rats (SHR). Therefore, we sought direct evidence of an interaction between AT1 and D5 receptors in RPT cells. D5 and AT1 receptors colocalized in WKY cells. Angiotensin II decreased D5 receptors in WKY cells in a time- and concentration-dependent manner (EC50=2.7x10(-9) M; t(1/2)=4.9 hours), effects that were blocked by an AT1 receptor antagonist (losartan). In SHR, angiotensin II (10(-8) M/24 hours) also decreased D5 receptors (0.96+/-0.08 versus 0.72+/-0.08; n=12) and to the same degree as in WKY cells (1.44+/-0.07 versus 0.92+/-0.08). However, basal D5 receptors were decreased in SHR RPT cells (SHR 0.96+/-0.08; WKY 1.44+/-0.07; n=12 per strain; P<0.05) and renal brush border membranes of SHR compared with WKY (SHR 0.54+/-0.16 versus WKY 1.46+/-0.10; n=5 per strain; P<0.05). Angiotensin II decreased AT1 receptor expression in WKY (1.00+/-0.04 versus 0.72+/-0.08; n=8; P<0.05) but increased it in SHR (0.96+/-0.04 versus 1.32+/-0.08; n=8; P<0.05). AT(1) and D5 receptors also interacted in vivo; renal D5 receptor protein was higher in mice lacking the AT1A receptor (AT1A-/-; 1.61+/-0.31; n=6) than in wild-type littermates used as controls (AT1A+/+; 0.81+/-0.08; n=6; P<0.05), and renal cortical AT1 receptor protein was higher in D5 receptor null mice than in wild-type littermates (1.18+/-0.08 versus 0.84+/-0.07; n=4; P<0.05). We conclude that D5 and AT1 receptors interact with each other. Altered interactions between AT1 and dopamine receptors may play a role in the pathogenesis of hypertension.