Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats.
Vascular resistance is increased in the kidneys of spontaneously hypertensive rats (SHR). Previous studies have demonstrated impaired vascular relaxations of mesenteric resistance arteries of SHR because of increased production of a cyclooxygenase-dependent endothelium-derived contracting factor. To test the hypothesis that altered endothelial function contributes to the enhanced constriction in kidneys of SHR, endothelium-mediated relaxations of renal resistance arteries from 5-6-week-old prehypertensive SHR and Wistar-Kyoto rats were compared in arteriographs. Acetylcholine induced endothelium-dependent contractions in SHR arteries, while potent endothelium-dependent relaxations were noted in renal arteries from Wistar-Kyoto rats. Inhibition of cyclooxygenase (indomethacin) or blockade of prostaglandin H2-thromboxane A2 receptors (SQ 29,548) blocked acetylcholine-induced contractions in SHR renal arteries; relaxations in SHR renal arteries after either treatment were similar to those observed in renal arteries from Wistar-Kyoto rats. NG-Nitro-L-arginine inhibited acetylcholine-mediated relaxations in both SHR and Wistar-Kyoto arteries. Endothelium-independent relaxations induced by verapamil were comparable in SHR and Wistar-Kyoto arteries. Thus, the impaired response to acetylcholine in SHR renal resistance arteries may result from the release of endothelium-derived cyclooxygenase products (prostaglandin H2 or thromboxane A2), which oppose endothelium-derived nitric oxide-mediated relaxation.
Dai
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FX
Department of Medicine, University of Kansas Medical Center, Kansas City 66103.
Skopec
J
J
Diederich
A
A
Diederich
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D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects*; D013928:Thromboxane A2 / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D014662:Vasoconstrictor Agents; D044262:Prostaglandin H2; D013928:Thromboxane A2