Both endothelium and afferent nerve endings play a role in acetylcholine-induced renal vasodilation

We investigated the nature and signaling pathways of endothelium- and sensory-nerve ending-derived substances involved in acetylcholine-induced vasodilation in rat isolated perfused kidney. Endothelial denudation by Triton X-100 (0.2%, 0.1 ml) or depletion of afferent nerve endings by capsaicin (10− 6 mol/l) attenuated acetylcholine-induced vasodilation. When these two agents were administered together, the response to acetylcholine was completely inhibited. CGRP1 receptor blocker CGRP 8–37 (10− 7 mol/l) and adenosine A2 receptor antagonist ZM 241 385 (10− 7 mol/l) inhibited acetylcholine-induced dilation. When indomethacin (10− 5 mol/l), a cyclooxygenase inhibitor, l-NOARG (10− 4 mol/l), a nitric oxide (NO) synthase inhibitor, and potassium chloride (30 mmol/l), to test EDHF response, were perfused simultaneously, the inhibition was greater than that was observed with each agent alone. Guanylate cyclase inhibitor ODQ (10− 5 mol/l) or protein kinase A inhibitor KT 5720 (5 × 10− 7 mol/l) inhibited acetylcholine-induced dilation. Gap junction uncoupler 18α-glycyrrhetinic acid (10− 4 mol/l) caused an uncontrollable increase in basal perfusion pressure making it impossible to test against acetylcholine-induced dilation. Our data suggest that NO, prostanoids, EDHF, and CGRP released from vascular endothelium and afferent nerve endings participate in acetylcholine-induced vasodilation and their signal transduction molecules include protein kinase A and guanylate cyclase.