Endothelial modulation of contractile responses in arteries from hypertensive rats.
The endothelium plays an important role in the circulation by modulating contractile responses of vascular smooth muscle. We designed this study to investigate the alterations of endothelial modulation in hypertension. Rings of femoral arteries were prepared from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), and changes in isometric tension were recorded. In rings with endothelium, norepinephrine (in either the presence or absence of yohimbine) evoked concentration-dependent contractions. Endothelium removal markedly enhanced the contraction; both the maximal response and sensitivity were increased, and these responses were less pronounced in SHR than WKY. In contrast to norepinephrine-induced contractions, the enhancement of prostaglandin F2 alpha-or serotonin-induced contractions after endothelium removal was small and comparable in WKY and SHR; sensitivity was increased, but the maximal response was not. N omega-Nitro-L-arginine methyl ester enhanced the contractions induced by these agonists in arteries with but not without endothelium and thereby abolished the enhancement of the contractions after endothelium removal. Thus, the endothelium plays an inhibitory role against contractions in rat femoral arteries by releasing nitric oxide, but the characteristics of the endothelial inhibition are not identical against various types of contractions. The negative endothelial modulation is more pronounced during alpha 1-adrenoceptor-mediated contractions than during contractions mediated by other receptors. The inhibitory role of the endothelium against alpha 1-adrenoceptor agonist-induced but not serotonin- or prostaglandin F2 alpha-induced contraction is impaired in hypertension.
Second Department of Internal Medicine, Nagoya City University Hospital, Japan.
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Y
Dohi
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Kojima
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Sato
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester