Lack of haemodynamic effects of nitric oxide on post‐capillary pulmonary hypertension induced by acute sino‐aortic denervation

The aims of the present experiments were to define a new experimental model of pulmonary hypertension induced by a post‐capillary mechanism and to assess the haemodynamic effects of nitric oxide on post‐capillary pulmonary hypertension. Cardiopulmonary variables of 28 male beagle dogs, anaesthetized with chloralose, 16 spontaneous breathing and 12 with assisted ventilation, were studied before and after sino‐aortic denervation (SAD). The haemodynamic effects of inhaled nitric oxide (25 p.p.m., 10 min), N ω ‐nitro‐ l ‐arginine methyl ester (20 mg kg −1 , i.v.), urapidil (0.5 mg kg −1 , i.v.) and propranolol (300 μg kg −1 , i.v.) were studied after SAD. SAD induced an acute and transient pulmonary hypertension, more marked in spontaneous breathing dogs. This pulmonary hypertension involved a post‐capillary mechanism, secondary to the left ventricular haemodynamic effects of the acute increase 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 strongly correlated with the variations of pulmonary capillary wedge pressure. Furthermore, no significant change in pulmonary vascular resistances was found after SAD or administration of α or β‐adrenoceptor antagonists. Inhaled nitric oxide did not reverse pulmonary hypertension induced by SAD. N ω ‐nitro‐ l ‐arginine methyl ester had no significant haemodynamic effect on pulmonary circulation. In conclusion, 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 leading to post‐capillary pulmonary hypertension.British Journal of Pharmacology (1997) 120 , 7–12; doi: 10.1038/sj.bjp.0700864