Contemporary activation of different endothelial receptors accounts for a reserve mechanism of nitric oxide-mediated relaxation.
The aim of this study was to investigate whether the inhibition of one of the endothelial receptor sites in the rat pulmonary artery (muscarinic, histaminergic, purinergic, alpha2-adrenergic) affects the NO-mediated relaxation induced by the activation of the other type of receptors. Acetylcholine (ACh)-, histamine (Hist)-, adenosine (Ade)-, and clonidine (Clon)-induced endothelium-dependent relaxations were reduced by the administration of specific antagonists of muscarinic, H1-histaminergic, purinergic or alpha2-adrenergic receptors, respectively. The inhibition of H1-histaminergic receptors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the relaxations to histamine, adenosine and clonidine. On the other hand, the relaxations induced by acetylcholine, histamine, adenosine or clonidine were regularly reduced by NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (10(-4) mol/l). These results suggest that the inhibition of NO-synthase abolished arterial relaxations induced by all agonists. After inhibition of one type of the endothelial receptors, the NO-dependent relaxation could still be evoked by activation of one of the others.
Kyselá
S
S
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. kysela@unpf.savba.sk
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D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D011956:Receptors, Cell Surface; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006632:Histamine; D000241:Adenosine; D003000:Clonidine; D000109:Acetylcholine