Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide production in 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 mechanically 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 comprised an initial peak followed by a lower plateau level. The increase in exhaled 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)-adrenoceptor agonist, also caused dose-dependent increases in exhaled NO. However, prenalterol was >100 times more potent than terbutaline. 5 Infusions of forskolin (0.01-0.03 mu mol kg(-1) min(-1)), an adenylate cyclase stimulator, elicited dose-dependent decreases in blood pressure and concomitant increases in heart rate but caused no alterations in exhaled NO. 6 Nimodipine, a L-type calcium channel blocker, antagonized the increases in exhaled NO in response to prenalterol infusions. 7 The increases in exhaled NO in response to adrenaline and prenalterol were also present in blood-free, buffer perfused lungs during constant-flow conditions. 8 These results demonstrate that pulmonary nitric oxide production can be enhanced by beta-adrenoceptor stimulation. Furthermore, the results indicate that the beta-adrenergic stimulation of pulmonary NO production is not critically dependent on cyclic AMP formation but may require intact calcium-channels.