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Contribution Of Nitric Oxide, Cyclic Gmp And K + Channels To Acetylcholine‐Induced Dilatation Of Rat Conduit And Resistance Arteries
Author(s) -
Woodman Owen L,
Wongsawatkul Orapin,
Sobey Christopher G
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03199.x
Subject(s) - acetylcholine , dilator , nitric oxide , phenylephrine , endocrinology , medicine , soluble guanylyl cyclase , nitric oxide synthase , chemistry , endothelium derived relaxing factor , vasodilation , aorta , guanylate cyclase , blood pressure
SUMMARY 1. We compared the effects of inhibiting nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and K + channel activation on dilator responses to acetylcholine (ACh) in rat resistance (hindquarters) and conduit arteries (thoracic aorta). 2. In rat perfused hindquarters, the NO synthase inhibitor N ω ‐nitro‐ L ‐arginine ( L ‐NNA; 1 mmol/L) partially inhibited the ACh‐induced dilatation and the combination of L ‐NNA + haemoglobin (Hb; 20 μ mol/L), a NO scavenger, did not further affect the response. Exposure to high K + (30 mmol/L) also inhibited the response to ACh and this response was further reduced by L ‐NNA + high K + . Surprisingly, when applied alone 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), an inhibitor of sGC, did not affect responses to ACh, whereas treatment with ODQ + high K + markedly impaired dilatation. 3. In aortic rings precontracted with phenylephrine (PE; 0.01–1 μ mol/L), the maximum relaxation to ACh was significantly reduced by L ‐NNA (0.1 mmol/L) and further inhibited by L ‐NNA + Hb (20 μ mol/L). At 10 μ mol/L, ODQ alone inhibited the maximum relaxation to ACh, which was further reduced by ODQ + high K + (30 mmol/L). High K + caused a smaller but significant inhibition of ACh‐induced relaxation. 4. These results suggest that NO and cGMP play a relatively greater role in ACh‐induced dilatation of the aorta compared with the hindquarters resistance vasculature and are consistent with the hypothesis that a non‐NO endothelium‐derived hyperpolarizing factor (endothelium‐derived hyperpolarizing factor; EDHF) makes a relatively greater contribution to dilatation of resistance vessels than in conduit arteries. The data suggest that when sGC is inhibited, a compensatory mechanism involving K + channel opening by NO can largely maintain ACh‐induced vasodilator responses of resistance vessels. Furthermore, when NO synthesis is blocked, a non‐ NO EDHF may play a role in ACh‐induced dilatation of the resistance vasculature.