Lack of haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension induced by acute sino-aortic denervation.
1. 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. 2. 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(omega)-nitro-L-arginine methyl ester (20 mg kg-1, i.v.), urapidil (0.5 mg kg-1-, i.v.) and propranolol (300 micrograms kg-1, i.v.) were studied after SAD. 3. 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 resistance was found after SAD or administration of alpha or beta-adrenoceptor antagonists. 4. Inhaled nitric oxide did not reverse pulmonary hypertension induced by SAD. N(omega)-nitro-L-arginine methyl ester had no significant haemodynamic effect of pulmonary circulation. 5. In conclusion, the lack of effect of inhaled nitric oxide and nitric synthase inhibitor on pulmonary circulation parameters SAD suggest that endothelium-derived oxide is not involved in the mechanisms leading to post-capillary pulmonary hypertension.
Galinier
M
M
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.
Rougé
P
P
Fourcade
J
J
Senard
J M
JM
Albenque
J P
JP
Balanescu
S
S
Doazan
J P
JP
Montastruc
J L
JL
Bounhoure
J P
JP
Montastruc
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003714:Denervation; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012849:Sinoatrial Node / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D010879:Piperazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011433:Propranolol; C015568:urapidil; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester