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 t he endothelial receptor sites in the rat pulmonary artery (muscarinic, hist aminergic, purinergic, alpha(2)-adrenergic) affects the NO-mediated relaxat ion 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 spe cific antagonists of muscarinic, HI-histaminergic, purinergic or alpha(2)-a drenergic receptors, respectively. The inhibition of HI-histaminergic recep tors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the rel axations to histamine, adenosine and clonidine. On the other hand, the rela xations induced by acetylcholine, histamine, adenosine or clonidine were re gularly reduced by NO-synthase inhibitor NG-nitro-L-arginine methyl ester ( 10(-4) mol/l). These results suggest that the inhibition of NO-synthase abo lished arterial relaxations induced by all agonists. After inhibition of on e type of the endothelial receptors, the NO-dependent relaxation could stil l be evoked by activation of one of the others.