Role of endothelium on alpha-adrenoceptor responsiveness and prostacyclin release from the mesenteric arterial bed of the rat.
1 Removal of endothelium from the isolated perfused mesenteric arterial bed (MAB) of the rat was associated with an increase in both basal release of prostacyclin and the pressor response to administered noradrenaline (NA). Under these conditions, the NA-stimulated release of prostacyclin was not altered. 2 In this preparation, prazosin, an alpha 1-adrenoceptor antagonist, caused a dose-dependent (10(-10)-10(-8) M) decrease in NA-stimulated prostacyclin production, whereas rauwolscine, an alpha 2-adrenoceptor antagonist (10(-8)-10(-7) M) had no significant effect. In addition, prazosin inhibited the NA-induced pressor responses (10(-10)-10(-8) M) while rauwolscine was only effective at a concentration of 10(-7) M. 3 L-NG mono-methyl-arginine (L-NMMA), an inhibitor of endothelial nitric oxide (NO) synthesis, was used to assess whether elimination of this substance was responsible for the increased basal release of prostacyclin and/or increased pressor responses observed after endothelium removal in the MAB. Concentrations of 3 x 10(-7)-3 x 10(-6) M of L-NMMA were without effect on either prostacyclin release or pressor responses to NA in the intact MAB. 4 These results indicate that in the endothelial denuded MAB, NA-induced release of prostacyclin is, mainly, alpha 1-adrenoceptor-mediated, in contrast to the intact MAB where it is alpha 2-adrenoceptor-dependent. It therefore appears that, in the MAB of the rat, the presence of endothelium obscures the alpha 1-mediated release of prostacyclin from vascular smooth muscle cells. In this preparation the endothelium may regulate both the release of prostacyclin and the contractile responses of the underlying smooth muscle via mechanisms independent of NO formation.
Pipili-Synetos
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Department of Pharmacology, University of Patras Medical School, Greece.
Sideri
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Maragoudakis
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology; D019323:omega-N-Methylarginine
D011942:Receptors, Adrenergic, alpha; D019323:omega-N-Methylarginine; D015016:Yohimbine; D001120:Arginine; D011464:Epoprostenol; D009638:Norepinephrine; D011224:Prazosin