title: The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery.
abstract: Urapidil (Eupressyl(®)) an antihypertensive drug acting as an α1 antagonist and a 5-HT1A agonist, may be of special interest in the treatment of hypertension associated with preeclamptic toxaemia and hypoxia-induced pulmonary arterial vasoconstriction. However, the effect of urapidil on vascular tone has been poorly investigated. Vascular reactivity was evaluated using pulmonary and coronary arteries from 36 pigs, aortae from 22 rats and 9 human pulmonary artery samples suspended in organ chambers. Concentration-relaxation curves either to urapidil, 5-HT, or the 5-HT1A receptor agonist 8-OH-DPAT were constructed after pre-contraction of rings. Pig pulmonary and coronary artery rings were contracted with U46619, a thromboxane mimetic, rat aortic rings with either endothelin-1 or phenylephrine, and human pulmonary artery rings with U46619 or phenylephrine. Urapidil markedly inhibited phenylephrine-induced contractions in rat aortic rings with and without endothelium with a more pronounced effect observed in rings without endothelium. Both 5-HT and 8-OH-DPAT failed to induce relaxation in rat aortic rings with an intact endothelium. 5-HT, but not urapidil and 8-OH-DPAT, induced a concentration-dependent relaxation in the porcine coronary and pulmonary artery rings with an intact endothelium (P<0.05). 5-HT and phenylephrine but not urapidil caused concentration-dependent contractions in human pulmonary artery rings. The present findings, while confirming that urapidil is a potent inhibitor of α1-adrenoceptor-induced contraction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone of the different types of arteries tested in response to urapidil. In addition, they indicate that urapidil seems to preferentially target arteries with endothelial dysfunction.
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, Strasbourg, France; Service d'Anesthésie-Réanimation Chirurgicale, Hôpitaux de Hautepierre, Strasbourg, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bopp
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Auger
authors.affiliation: Service d'Anesthésie-Réanimation Chirurgicale, Hôpitaux de Hautepierre, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Diemunsch
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, Strasbourg, France. Electronic address: valerie.schini-kerth@unistra.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Schini-Kerth
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C015568:urapidil; D001920:Bradykinin
keywords: 5-HT1A agonist; Alpha-1 adrenoceptor antagonist; Antihypertensive drug; Urapidil; Vascular reactivity