LACK OF HEMODYNAMIC-EFFECTS OF NITRIC-OXIDE ON POST-CAPILLARY PULMONARY-HYPERTENSION INDUCED BY ACUTE SINOAORTIC DENERVATION

1 The aims of the present experiments were to define a new experimenta l model of pulmonary hypertension induced by a post-capillary mechanis m and to assess the haemodynamic effects of nitric oxide on post-capil lary pulmonary hypertension. 2 Cardiopulmonary variables of 28 male be agle dogs, anaesthetized with chloralose, 16 spontaneous breathing and 12 with assisted ventilation, were studied before and after sine-aort ic denervation (SAD). The haemodynamic effects of inhaled nitric oxide (25 p.p.m., 10 min), N-omega-nitro-L-arginine methyl ester (20 mg kg( -1), i.v.), urapidil (0.5 mg kg(-1), i.v.) and propranolol (300 mu g k g(-1), i.v.) were studied after SAD. 3 SAD induced an acute and transi ent pulmonary hypertension, more marked in spontaneous breathing dogs. This pulmonary hypertension involved a post-capillary mechanism, seco ndary to the left ventricular haemodynamic effects of the acute increa se of left ventricular after-load induced by systemic hypertension. In fact, the increase of mean pulmonary arterial pressure after SAD and the decrease of this parameter after urapidil or propranolol were stro ngly correlated with the Variations of pulmonary capillary wedge press ure. Furthermore, no significant change in pulmonary vascular resistan ces was found after SAD or administration of alpha or beta-adrenocepto r antagonists. 4 Inhaled nitric oxide did not reverse pulmonary hypert ension induced by SAD. N-omega-nitro-L-arginine methyl ester had no si gnificant haemodynamic effect on pulmonary circulation. 5 In conclusio n the lack of effect of inhaled nitric oxide and nitric oxide synthase inhibitor on pulmonary circulation parameters after SAD suggests that endothelium-derived nitric oxide is not involved in the mechanisms le ading to post-capillary pulmonary hypertension.