Related Experiment Videos
Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension
S Taddei1, A Virdis, L Ghiadoni
1I Clinica Medica, University of Pisa, Italy.
Insights
In essential hypertension, cyclooxygenase inhibition restores nitric oxide-mediated vasodilation. This suggests that cyclooxygenase-dependent substances impair nitric oxide production, impacting blood vessel function.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Hypertension Research
Background:
- Essential hypertension is characterized by impaired nitric oxide (NO)-mediated vasodilation.
- The role of cyclooxygenase (COX) constrictor substances in this impairment is not fully understood.
Purpose of the Study:
- To investigate whether COX constrictor substances impair NO-mediated vasodilation in essential hypertension.
- To determine the effect of COX inhibition on NO-mediated vasodilation in hypertensive patients.
Main Methods:
- Forearm blood flow was measured using strain-gauge plethysmography in normotensive and hypertensive subjects.
- Intrabrachial infusions of acetylcholine, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), indomethacin (a COX inhibitor), and L-arginine were administered.
- Vasodilation responses were assessed under basal conditions and during inhibitor/substrate infusions.
Main Results:
- In hypertensive patients, vasodilation to acetylcholine was not affected by L-NMMA but was significantly enhanced by indomethacin.
- Indomethacin also restored the inhibitory effect of L-NMMA on acetylcholine-induced vasodilation in hypertensives.
- In normotensive subjects, L-NMMA blunted vasodilation, an effect not altered by indomethacin.
Conclusions:
- Cyclooxygenase inhibition restores nitric oxide-mediated vasodilation in essential hypertension.
- These findings suggest that COX-dependent substances impair NO production or bioavailability in hypertension.
- Targeting the COX pathway may represent a therapeutic strategy for improving vascular function in hypertensive individuals.
Abstract:
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.