Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension.
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 micrograms.100 mL-1.min-1) in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA; 100 micrograms.100 mL-1.min-1), a nitirc oxide synthase inhibitor, or indomethacin (50 micrograms.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 micrograms.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 acetylcholine (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.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy.
Virdis
A
A
Ghiadoni
L
L
Magagna
A
A
Salvetti
A
A
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin