Changes in the endothelial cyclooxygenase pathway in resistance arteries of spontaneously hypertensive rats.
Vasodilator responses to adenosine and acetylcholine (ACh) were studied in ring preparations of mesenteric resistance arteries of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Adenosine (10(-7)-3 x 10(-4) M) caused relaxations in rings with endothelium. The relaxation was more pronounced in WKY than in SHR. Removal of the endothelium in WKY, but not in SHR, reduced the relaxation. In rings without endothelium, the relaxation was identical in the two strains. In WKY, the cyclooxygenase inhibitor meclofenamic acid attenuated the relaxation to adenosine in rings with endothelium but not in rings without endothelium. With meclofenamic acid, the relaxation was identical in WKY arteries with and without endothelium. ACh (10(-9)-10(-4) M) evoked endothelium-dependent relaxations in WKY. In contrast, in SHR the muscarinic agonist evoked contractions at higher concentrations (10(-6)-10(-4) M), whereas lower concentrations of ACh caused relaxations similar to those observed in WKY. The contraction in SHR was completely inhibited by meclofenamic acid, and with meclofenamic acid the relaxation to ACh was identical in WKY and SHR. Thus, adenosine evokes endothelium-dependent (through release of cyclooxygenase product) and endothelium-independent relaxations and ACh evokes endothelium-dependent relaxations in rat mesenteric resistance arteries. In SHR, the endothelium-dependent responses to the agonists are altered owing to the changes in the endothelial cyclooxygenase pathway.
Takase
H
H
Second Department of Internal Medicine, Nagoya City University Hospital, Japan.
Dohi
Y
Y
Kojima
M
M
Sato
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology*; D006973:Hypertension / Q000201:enzymology*; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D008469:Meclofenamic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D000241:Adenosine; D000109:Acetylcholine