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.

Passive smoking impairs endothelium-dependent relaxation of isolated rabbit arteries.

The aim of the present study was to examine the effect of prolonged passive smoking (lasting 3 weeks) on plasma catecholamine levels and reactivity of isolated rabbit arteries. Plasma noradrenaline, adrenaline and dopamine levels were determined radioenzymatically. Isolated rings of the thoracic aorta and carotid artery were suspended in organ chambers and connected to a force transducer for the recording of isometric tension. Plasma noradrenaline levels were found to be significantly elevated in rabbits subjected to passive smoking for 3 weeks. Plasma adrenaline and dopamine levels were not changed. Transmural nerve stimulation of arterial rings evoked frequency-dependent contractions. Prolonged passive smoking did not affect neurogenic contractions of the arteries tested. On the other hand, endothelium-dependent relaxations of phenylephrine-precontracted arteries were significantly impaired. Furthermore, hypertrophy of the left ventricle was observed. In conclusion, passive smoking impairs endothelium-dependent relaxations but not neurogenic contractions of systemic arteries. The impaired relaxations of arteries may be, at least in part, mediated through the degradation of released nitric oxide by superoxide anions derived from cigarette smoke.

[The role of endothelial nitric oxide in neurogenic contractions of the carotid artery in rabbits during cooling]. / Uloha endotelového oxidu dusnatého v neurogénnych kontrackciách a. carotis králika pocas ochladenia.

The role of endothelial nitric oxide in contractions induced by endogenous noradrenaline released by transmural nerve stimulation (TNS) and by exogenous noradrenaline (NA) was studied in isolated rings of rabbit carotid artery during cooling. At 37 degrees C, TNS produced frequency-dependent contractions of artery. Endothelium removal or inhibition of nitric oxide synthase by NG-nitro-L-arginine methyl ester (L-NAME) significantly enhanced TNS-induced contractions. The magnitude of maximal contraction to exogenous NA was increased in L-NAME-treated intact rings. Cooling the incubation bath from 37 degrees C to 26 degrees C increased the magnitude of neurogenic contractions in intact rings. L-NAME increased further the magnitude of neurogenic contractions at 26 degrees C in intact, but not in denuded arterial rings. Similarly, L-NAME increased contractions induced by exogenous NA during cooling. The results suggest that the response of the carotid artery to noradrenergic stimulation is modulated by nitric oxide originating from endothelial cells at normal as well as reduced temperature. (Tab. 1, Fig. 6, Ref. 19.)

Histamine H1-receptor antagonists do not prevent the appearance of endothelium-dependent relaxation to acetylcholine in rat pulmonary artery.

The purpose of this study was to determine the relaxant effects of acetylcholine after inhibition of vascular histaminergic receptors. In isolated rings of the rat pulmonary artery precontracted by phenylephrine (10(-5) mol/l) both histamine (10(-7) to 10(-4) mol/l) and acetylcholine (10(-8) to 3 x 10(-5) mol/l) produced concentration-dependent relaxations. The arterial relaxations induced by either histamine or acetylcholine were markedly reduced or abolished by administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (10(-5) mol/l). Relaxant responses to histamine were not influenced by cimetidine, histamine H2-receptor antagonist, but were significantly decreased or abolished by treatment with chlorphenyramine or diphenhydramine, histamine H1-receptor antagonists. On the other hand, chlorphenyramine and diphenhydramine did not prevent the appearance of endothelium-dependent relaxation to acetylcholine. The results suggest that relaxation to histamine in the rat pulmonary artery is mediated by H1-histaminergic receptors and their inactivation does not interfere with the endothelial capability to produce and/or release nitric oxide by the activation of other types of receptors.