(Hypertension. 1997;29:274.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Cyclooxygenase Inhibition Restores Nitric Oxide Activity in Essential Hypertension
From I Clinica Medica, University of Pisa, Italy.
Correspondence to Stefano Taddei, MD, I Clinica Medica, University of Pisa, Via Roma, 67, 56100 Pisa, Italy
To evaluate whether cyclooxygenase constrictor substances can impair nitric oxide-mediated vasodilation in essential hypertension, in seven normotensive subjects (43.3±4.1 years; BP, 117±6/81±2 mm Hg) and seven essential hypertensive patients (47.1±5.2 years; BP, 151±8/98±4 mm Hg) we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15,0.45, 1.5, 4.5, 15 µg·100 mL-1·min-1) in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA; 100 µg·100 mL-1·min-1), a nitric oxide synthase inhibitor, or indomethacin (50 µg·100 mL-1·min-1), a cyclooxygenase inhibitor, or simultaneous indomethacin and L-NMMA. In normotensives, vasodilation to acetylcholine was blunted by L-NMMA (maximum flow increase: 671±64% and 386±42%, respectively; P<.01), and this effect was unchanged by indomethacin. In contrast, in hypertensive patients, vasodilation to acetylcholine (maximum flow increase: 458±33%) was unchanged by L-NMMA. Indomethacin significantly (P<.01) increased the response to acetylcholine (maximum flow increase: 635±53%) and restored the inhibitory effect of L-NMMA (maximum flow increase: 445±36%; P<.01 versus indomethacin alone). In an adjunctive seven normotensives (51.4±4.2 years; BP, 114±5/79±3 mm Hg) and seven essential hypertensives (53.2±7.6 years; BP, 153±9/100±3 mm Hg) we repeated the same protocol by replacing L-NMMA with L-arginine (200 µg·100 mL-1·min-1), the substrate for NO synthase. In normotensives, vasodilation to acetylcholine was increased by L-arginine (maximum flow increase: 539±48% and 806±61%, respectively) and this effect was unchanged by indomethacin. In hypertensive patients, vasodilation to acetyl-choline (maximum flow increase: 339±32%) was unchanged by L-arginine but was significantly (P<.01) increased by indomethacin (maximum flow increase: 592±38%). Moreover, indomethacin restored the facilitatory effect of L-arginine (maximum flow increase: 804±56%; P<.01 versus indomethacin alone). Therefore, cyclooxygenase inhibition restores nitric oxide-mediated vasodilation in essential hypertension, suggesting that cyclooxygenase-dependent substances can impair nitric oxide production.
Key Words: hypertension • endothelium • nitric oxide • endothelium-derived factors • indomethacin
Abbreviations: BP = blood pressure • EDCF = endothelium-derived contracting factor(s) • FBF = forearm blood flow • L-NMMA = NG-monomethyl-L-arginine • NO = nitric oxide • NS = not significant
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