Endothelial dysfunction of resistance arteries of spontaneously hypertensive rats.
Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of endothelium-derived, cyclooxygenase-dependent contractile factors. The objectives of the present study were to determine whether alterations in endothelial function precede the development of hypertension in SHRs and to characterize the contractile factor(s) produced by SHR endothelial cells. Mean systolic blood pressures were minimally (6 mm Hg) higher at 4 weeks of age in SHRs than in Wistar-Kyoto (WKY) rats. Endothelium-mediated relaxations of mesenteric and renal resistance arteries from SHRs and WKY rats were compared in myographs and arteriographs in paired experiments. Acetylcholine (ACh, 10(-9) to 10(-7) M) induced endothelium-dependent relaxations in precontracted mesenteric and renal resistance arteries that were similar in SHRs and WKY rats. At higher concentrations of ACh (10(-6) to 10(-5) M), relaxations were replaced by contractile responses in SHR but not in WKY rat resistance arteries. The contractile responses were endothelium dependent and were inhibited by indomethacin in both mesenteric and renal arteries. Thus, endothelial dysfunction precedes and may contribute to the development of accelerated hypertension in SHRs. SQ 29548, a prostaglandin H2 (PGH2)-thromboxane A2 receptor antagonist, blocked the contractile responses in renal but not in mesenteric resistance arteries. The contractile responses in mesenteric arteries were inhibited by 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide production via the cyclooxygenase pathway. We conclude from these data that the endothelium-derived contracting factor (EDCF) produced in SHR renal arteries is most likely PGH2 whereas the contractile factor produced in mesenteric arteries is superoxide.
D000109:Acetylcholine / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011463:Prostaglandins H; D013481:Superoxides; D044262:Prostaglandin H2; D013928:Thromboxane A2; C045749:SQ 29548; D000109:Acetylcholine; D007213:Indomethacin; D000640:Amitrole