title: Cyclic GMP-independent mechanisms of nitric oxide-induced vasodilation.
abstract: 1. The aim of the present study was to test in vitro if NO acts through a cyclic GMP-independent mechanism to activate Ca2+-dependent potassium channels (K+(Ca)), leading to membrane hyperpolarization and vasodilation in rat tail artery. 2. Acetylcholine and sodium nitroprusside stimulated a significant increase in cyclic GMP (190+/-23 and 180+/-15 pmol/g, respectively) compared with agonist-free conditions (132+/-15 and 130+/-15 pmol/g, respectively); these agonist-mediated increases in cyclic GMP were completely abolished by treatment with the guanylate cyclase inhibitor methylene blue (122+/-10 and 60+/-8 pmol/g, respectively). 3. In contrast, relaxation to acetylcholine (10(-7) mol/l; 61+/-3%) and sodium nitroprusside (10(-8) mol/l; 97+/-1%) were significantly, but not completely, attenuated by methylene blue (30+/-5 and 79+/-3%, respectively); maximum relaxation to sodium nitroprusside (10(-7) mol/l) was unaffected by methylene blue. 4. Depolarization-induced contraction of vessels with KCl inhibited relaxation to both acetylcholine (10(-7) mol/l; 18+/-4%) and sodium nitroprusside (10(-8) mol/l; 57+/-7%). Furthermore, the specific K+(Ca) antagonist charybdotoxin significantly inhibited relaxation to sodium nitroprusside (10(-8) mol/l; 52+/-7%). 5. An additive inhibitory effect on relaxation to sodium nitroprusside (10(-8) mol/l) was observed with a combination of methylene blue and KCl (26+/-6%) or charybdotoxin (34+/-3%). 6. These data suggest that NO stimulates membrane hyperpolarization via K+(Ca) activation, in addition to guanylate cyclase, to cause relaxation in rat tail artery.
authors.affiliation: Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA. chetan-goud@uiowa.edu
authors.forename: C
authors.initials: C
authors.lastname: Goud
authors.forename: A
authors.initials: A
authors.lastname: DiPiero
authors.forename: W E
authors.initials: WE
authors.lastname: Lockette
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
authors.forename: J R
authors.initials: JR
authors.lastname: Charpie
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018999:Charybdotoxin; D009599:Nitroprusside; D009569:Nitric Oxide; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine