Differential Reactivity of Cortical and Juxtamedullary Glomeruli to Adenosine-1 and Adenosine-2 Receptor Stimulation and Angiotensin-Converting Enzyme Inhibition

Abstract

A recently developed modification of the technique of the split hydronephrotic rat kidney enables intravital assessment of vascular reactivity of cortical and juxtamedullary (JM) glomeruli and their vascular network. Effects of the adenosine-1 receptor agonist N6 -cyclohexyladenosine (CHA) and the adenosine-2 receptor agonist N-ethylcarboxamide-adenosine (NECA) on these renovascular structures were examined before and after angiotensin II-converting enzyme (CE) inhibition by quinapril (0.9 mg kg-1 iv). CE inhibition was undertaken to test for an interdependence of adenosine and angiotensin II, as we have previously demonstrated for cortical glomeruli and CHA. In the first series of experiments (n = 7), CHA (in local dosages from 10-8 to 10-6 mole liter-1 produced a dose-dependent vasoconstriction of all preglomerular vessels and a decrease of cortical glomerular blood flow that was markedly attenuated by CE inhibition. In JM glomeruli, CHA also led to a dose-dependent vasoconstriction, but these effects were, on the contrary, unchanged or even increased by CE inhibition. In the second series (n = 6), NECA (in local dosages from 10-8 to 10-5 mole liter-1) led to a vasodilation and an increase in glomerular blood flow both before and after CE inhibition in both cortical and JM glomeruli. The reactions induced by NECA alone in the principal preglomerular vessel segments were significantly larger than those under NECA and simultaneous CE inhibition, thereby demonstrating an attenuation of NECA effects induced by CE inhibition. In additional series, we demonstrated a dose-dependent vasoconstriction of all pre-and postglomerular cortical vessel segments by local application of angiotensin I (dosage 10-8 to 10-6 mole liter-1) and the abolition of these effects by quinapril. Our findings demonstrate a differential reactivity of cortical and juxtamedullary glomeruli to adenosine receptor agonists and, additionally, an interdependence of adenosine-and angiotensin II-induced renovascular effects.