Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension

被引:165
作者
Taddei, S
Virdis, A
Ghiadoni, L
Magagna, A
Salvetti, A
机构
关键词
hypertension; endothelium; nitric oxide; endothelium-derived factors; indomethacin;
D O I
10.1161/01.HYP.29.1.274
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 mu g . 100 ml(-1) . min(-1)) in basal conditions, during infusion of N-G-monomethyl-L-arginine (L-NMMA; 100 mu g . 100 mL(-1) . min(-1)), a nitric oxide synthase inhibitor, or indomethacin (50 mu g . 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 mu g . 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.
引用
收藏
页码:274 / 279
页数:6
相关论文
共 31 条
  • [1] CALVER A, 1992, J HYPERTENS, V10, P1025
  • [2] ROLE OF SUPEROXIDE ANIONS IN THE MEDIATION OF ENDOTHELIUM-DEPENDENT CONTRACTIONS
    COSENTINO, F
    SILL, JC
    KATUSIC, ZS
    [J]. HYPERTENSION, 1994, 23 (02) : 229 - 235
  • [3] IMPAIRED ENDOTHELIUM-DEPENDENT RELAXATIONS IN HYPERTENSIVE RESISTANCE ARTERIES INVOLVE CYCLOOXYGENASE PATHWAY
    DIEDERICH, D
    YANG, ZH
    BUHLER, FR
    LUSCHER, TF
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (02): : H445 - H451
  • [4] THE OBLIGATORY ROLE OF ENDOTHELIAL-CELLS IN THE RELAXATION OF ARTERIAL SMOOTH-MUSCLE BY ACETYLCHOLINE
    FURCHGOTT, RF
    ZAWADZKI, JV
    [J]. NATURE, 1980, 288 (5789) : 373 - 376
  • [5] SUPEROXIDE ANION IS INVOLVED IN THE BREAKDOWN OF ENDOTHELIUM-DERIVED VASCULAR RELAXING FACTOR
    GRYGLEWSKI, RJ
    PALMER, RMJ
    MONCADA, S
    [J]. NATURE, 1986, 320 (6061) : 454 - 456
  • [6] PROSTAGLANDIN-H2 MAY BE THE ENDOTHELIUM-DERIVED CONTRACTING FACTOR RELEASED BY ACETYLCHOLINE IN THE AORTA OF THE RAT
    KATO, T
    IWAMA, Y
    OKUMURA, K
    HASHIMOTO, H
    ITO, T
    SATAKE, T
    [J]. HYPERTENSION, 1990, 15 (05) : 475 - 481
  • [7] SUPEROXIDE ANION IS AN ENDOTHELIUM-DERIVED CONTRACTING FACTOR
    KATUSIC, ZS
    VANHOUTTE, PM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (01): : H33 - H37
  • [8] DIFFERENT MECHANISMS OF ENDOTHELIAL DYSFUNCTION WITH AGING AND HYPERTENSION IN RAT AORTA
    KUNG, CF
    LUSCHER, TF
    [J]. HYPERTENSION, 1995, 25 (02) : 194 - 200
  • [9] INDIRECT EVIDENCE FOR RELEASE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN HUMAN FOREARM CIRCULATION INVIVO - BLUNTED RESPONSE IN ESSENTIAL-HYPERTENSION
    LINDER, L
    KIOWSKI, W
    BUHLER, FR
    LUSCHER, TF
    [J]. CIRCULATION, 1990, 81 (06) : 1762 - 1767
  • [10] Luscher T.F., 1990, ENDOTHELIUM MODULATO, V001-228