RENAL ARTERIOLAR ANGIOTENSIN RESPONSES DURING VARIED ADENOSINE RECEPTOR ACTIVATION

We performed experiments to test the hypothesis that endogenous adenos ine acts as an essential cofactor required for eliciting angiotensin I I (Ang II)-induced afferent and/or efferent arteriolar vasoconstrictio n. Enalaprilat (2 mg IV) was administered to anesthetized rats to redu ce endogenous Ang II levels. Kidneys and blood were harvested from the se animals and used for study of renal microvascular function using th e in vitro blood-perfused juxtamedullary nephron technique. Arteriolar inside diameter was monitored videomicroscopically in (1) normal kidn eys, (2) kidneys subjected to adenosine receptor blockade (100 mu mol/ L 1,3-dipropyl-8-p-sulfophenylxanthine), and (3) kidneys continuously exposed to 1 mu mol/L adenosine. Under resting conditions, arteriolar diameters were similar in all three groups of kidneys, averaging 24.8/-1.0 mu m (n=23) in afferent arterioles and 24.0+/-0.9 mu m (n=16) in efferent arterioles. In normal kidneys, adenosine (10 mu mol/L) decre ased both afferent (10.2+/-2.0%) and efferent (6.5+/-0.8%) diameters, an effect that was absent in kidneys subjected to adenosine receptor b lockade. Ang II (10 pmol/L to 100 nmol/L) elicited dose-dependent vaso constriction of both vascular segments in normal kidneys. At a concent ration of 100 nmol/L, Ang II decreased afferent diameter by 36.8+/-8.5 % and efferent diameter by 30.8+/-9.6%. Neither afferent nor efferent arteriolar Ang II dose-response relations were significantly different in kidneys treated with low-dose adenosine or the adenosine receptor blocker. These observations refute the hypothesis that a receptor-medi ated action of adenosine is required for Ang II-induced constriction o f juxtamedullary afferent or efferent arterioles. Furthermore, subcons trictor adenosine levels do not potently modulate renal arteriolar vas oconstrictor responses to Ang II.