Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve cyclooxygenase pathway.
Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing (EDRF) and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. Mesenteric resistance arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were suspended in a myograph filled with physiological salt solution (37 degrees C; 95% O2-5% CO2). In WKY rings contracted with norepinephrine, acetylcholine (10(-9)-10(-4) M) evoked endothelium-dependent relaxations (88 +/- 2%, IC50 7.3 +/- 0.1; n = 31). Hemoglobin (10(-5) M) but not meclofenamate (10(-5) M) reversed the relaxations delineating EDRF as the mediator. Nitric oxide (3 X 10(-9)-10(-5) M) induced comparable relaxations as acetylcholine. In SHRSP, relaxations to acetylcholine but not those to nitric oxide were impaired (61 +/- 5%, IC50 greater than 6.6 +/- 0.4; n = 24; P less than 0.005). In SHRSP, meclofenamate but not the thromboxane synthetase inhibitor CGS 13080 normalized endothelium-dependent relaxations. Relaxations to sodium nitroprusside were enhanced in SHRSP both in rings with and without endothelium. Thus our results are compatible with the concept that endothelium-dependent relaxations in resistance arteries are mediated by nitric oxide. In SHRSP, endothelium-dependent relaxations are impaired because of a cyclooxygenase-dependent substance interfering with the release and/or action of EDRF.
Diederich
D
D
Department of Medicine, University Hospital, Basel, Switzerland.
Yang
Z H
ZH
Bühler
F R
FR
Lüscher
T F
TF
D000818:Animals; D001158:Arteries / Q000201:enzymology / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000209:etiology; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009574:Nitro Compounds / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D009574:Nitro Compounds; D014665:Vasodilator Agents; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine