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Role of nitric oxide in isoprenaline and sodium nitroprusside‐induced relaxation in human hand veins
Author(s) -
Chalon Stephan,
Tejura Bina,
Moreno Jr Heitor,
Urae Akinori,
Blaschke Terrence F.,
Hoffman Brian B.
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00863.x
Subject(s) - sodium nitroprusside , isoprenaline , bradykinin , phenylephrine , chemistry , vasodilation , nitric oxide , agonist , medicine , endocrinology , sodium , pharmacology , anesthesia , biochemistry , blood pressure , receptor , stimulation , organic chemistry
Aims Recent reports, largely in animal models, have suggested that either inhibition of nitric oxide (NO) synthase or endothelium removal in arteries inhibits the response to isoprenaline, a β‐adrenoceptor agonist, and also enhances the response to sodium nitroprusside, a nitrovasodilator. This in vivo study was designed to determine whether N G ‐monomethyl‐l‐arginine (l‐NMMA), an inhibitor of NO synthesis, influences relaxation of human hand veins mediated by isoprenaline or by sodium nitroprusside.Methods Using the dorsal hand vein technique, full dose‐response curves to bradykinin (0.27–278 ng min −1 , n=6), isoprenaline (2.12–271 ng min −1 , n=8) and sodium nitroprusside (0.01–634 ng min −1 , n=7) were generated on separate occasions before and after l‐NMMA co‐infusion (50 μg min −1 ).Results In veins preconstricted with the α 1 ‐adrenoceptor‐selective agonist phenylephrine, the three vasodilators induced maximal responses (E max ) of 119±35, 72±18 and 103±17%, respectively. l‐NMMA inhibited relaxation to bradykinin by 64% (P=0.014) but did not influence relaxation induced by isoprenaline. The sensitivity to sodium nitroprusside was significantly enhanced by l‐NMMA co‐infusion (concentration shift of 2.3, P =0.031).Conclusions We conclude that in human veins, spontaneously released NO does not play a major role in isoprenaline‐induced relaxation. Our results also suggest that the effects of sodium nitroprusside in this vascular bed may be attenuated by endothelium‐derived NO.