title: Both endothelium and afferent nerve endings play a role in acetylcholine-induced renal vasodilation.
abstract: 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 A(2) 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 (5x10(-7) mol/l) inhibited acetylcholine-induced dilation. Gap junction uncoupler 18alpha-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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey. iay@partners.org
authors.forename: Ilknur
authors.initials: I
authors.lastname: Ay
authors.forename: Meral
authors.initials: M
authors.lastname: Tuncer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; C097270:ZM 241385; D019335:Nitroarginine; D009569:Nitric Oxide; D017830:Octoxynol; D052250:Nitric Oxide Synthase Type III; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D006034:Glycyrrhetinic Acid; D002211:Capsaicin; D007213:Indomethacin