Synergistic effects of angiotensin and adenosine in the renal microvasculature.

Experiments were performed in the in situ kidney of rats and in isolated afferent arterioles of the rabbit to study the interaction between angiotensin II and adenosine in producing afferent arteriolar vasoconstriction. In the intact rat kidney, we observed that 1) peritubular infusion of the adenosine1-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX, 10(-4) M) blocked the fall in stop-flow pressure (PSF) induced by angiotensin II (5 x 10(-7) M) but not that caused by vasopressin (10(-5) M) or norepinephrine (10(-5) M), 2) peritubular infusion of saralasin (5 x 10(-5) M) attenuated the fall in PSF caused by N6-cyclohexyladenosine (CHA, 10(-5) M) 3) the fall in PSF following luminal application of CHA (10(-5) M) was reduced in angiotensin II-depleted states (volume expansion and converting enzyme inhibition) and this could be reversed by infusion of low doses of angiotensin II, and 4) the reduction in PSF in response to luminal infusion of CHA was augmented in a greater-than-additive fashion when angiotensin was simultaneously administered at low intravenous infusion rates. In isolated afferent arterioles of the rabbit, we noted that 1) addition of 10(-5) M CPX to the bath significantly blunted the constrictor effect of angiotensin II (10(-8) M), 2) presence of the converting enzyme inhibitor quinaprilate (10(-7) M) caused a right shift in the constrictor-response curve to increasing concentrations of CHA (10(-9)-10(-5) M) but 10(-5) M saralasin did not affect vasoconstriction caused by 10(-6) M adenosine, 3) simultaneous administration of submaximal constrictor doses of angiotensin II (10(-10) M) and adenosine (10(-6) M) produced vasoconstriction that was greater than additive, and 4) 10(-5) M CHA and angiotensin II (10(-7) M) constricted afferent arterioles after removal of the glomerulus, whereas either agent alone had no constrictor effect in this preparation. Our results suggest that adenosine and angiotensin cooperate in a mutually dependent and synergistic fashion in producing afferent arteriolar vasoconstriction.