Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide productionin the rabbit

1 Nitric oxide (NO) is continuously produced in the lung and is present in exhaled air. We examined the effect of beta-adrenoceptor stimulation on the production of pulmonary NO in rabbits. 2 Exhaled NO was measured by chemiluminescence in anaesthetized and mechani cally ventilated rabbits and in buffer-perfused rabbit lungs. 3 Intravenous infusions of adrenaline (0.1-10 mu g kg(-1) min(-1)) elicited dose-dependent increases in exhaled NO. The increases in exhaled NO compri sed an initial peak followed by a lower plateau level. The increase in exha led NO was inhibited by propranolol (1 mg kg(-1)) but not by phentolamine ( 1 mg kg(-1)). 4 Prenalterol, a beta(1)-adrenoceptor agonist, and terbutaline, a beta(2)-a drenoceptor agonist, also caused dose-dependent increases in exhaled NO. Ho wever, prenalterol was >100 times more potent than terbutaline. 5 Infusions of forskolin (0.01-0.03 mu mol kg(-1) min(-1)), an adenylate cy clase stimulator, elicited dose-dependent decreases in blood pressure and c oncomitant increases in heart rate but caused no alterations in exhaled NO. 6 Nimodipine, a L-type calcium channel blocker, antagonized the increases i n exhaled NO in response to prenalterol infusions. 7 The increases in exhaled NO in response to adrenaline and prenalterol wer e also present in blood-free, buffer perfused lungs during constant-flow co nditions. 8 These results demonstrate that pulmonary nitric oxide production can be e nhanced by beta-adrenoceptor stimulation. Furthermore, the results indicate that the beta-adrenergic stimulation of pulmonary NO production is not cri tically dependent on cyclic AMP formation but may require intact calcium-ch annels.