Hypoxic vasoconstriction (HPV) has been shown to consist of a biphasic contraction change. The first phase of the hypoxic response peaks at approximately five minutes. The second phase is at about 30 minutes. The force of contraction of both phases of HPV were found to be significantly greater in pulmonary resistance vessels (PRV) than in pulmonary artery (PA) (P<0.01). The endothelium modulates the hypoxic response, especially of the second phase of HPV (68 % reduction in PRV) (P<0.05). In Ca2+-free solution, the first peak and the second peak of HPV were reduced to 11 and 32 % contraction in PRV and to 26 and 21 % contraction in PA. A calcium channel antagonist (amlodipine) caused significant dose-dependent inhibition of the first phase of HPV (P=0.001), with a significantly greater effect on PRV compared to PA (P<0.01). Levcromakalim caused a dose- dependent inhibition of HPV in PRV (58 % at 10 /utA). In contrast, HPV in PA was not significantly inhibited by levcromakalim. In conclusion, this study has confirmed that hypoxia induces a biphasic contractile response in isolated pulmonary arteries requiring extracellular calcium. Both amlodipine and levcromakalim inhibit hypoxic pulmonary vasoconstriction and these agents may be of value in the treatment of pulmonary hypertension.
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, a 2-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 a 2-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 NG-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., S. Kyselá, J. Török., and Obsahuje bibliografii
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/1) both histamine (10-7 to 10-4 mol/1) and acetylcholine (10-8 to 3xl0-5 mol/1) 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/1). 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 Hi-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 Hi-histaminergic receptors and their inactivation docs not interfere with the endothelial capability to produce and/or release nitric oxide by the activation of other types of receptors.
The aim of this study was to determine the relative contribution of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in histamine-induced relaxation of isolated pulmonary artery from normotensive and hypertensive rats. The hypertension was induced by oral administration of NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 50 mg/kg/day) to normotensive rats for 8 weeks. In phenylephrine-precontracted arterial rings the histamine-induced relaxation was significantly reduced in L-NAME-treated rats compared to the controls. Indomethacin (cyclooxygenase inhibitor) and glibenclamide (ATP-sensitive K+-channel blocker) did not inhibit the relaxation response in either control or hypertensive rats. On the other hand, tetraethylammonium (TEA), a K+-channel blocker with a broad specificity, significantly reduced histamine-induced relaxation in the pulmonary artery from both groups examined. The TEA-resistant relaxation was completely abolished by additional administration of L-NAME to the incubation medium. The results indicate that histamine-induced relaxation of the pulmonary artery in both normotensive and hypertensive rats is mediated mainly by nitric oxide, whereas EDHF seems to play a minor role., J. Török., and Obsahuje bibliografii