Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide production in the rabbit.
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. Exhaled NO was measured by chemiluminescence in anaesthetized and mechanically ventilated rabbits and in buffer-perfused rabbit lungs. Intravenous infusions of adrenaline (0.1-10 microg 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)). Prenalterol, a beta1-adrenoceptor agonist, and terbutaline, a beta2-adrenoceptor agonist, also caused dose-dependent increases in exhaled NO. However, prenalterol was >100 times more potent than terbutaline. Infusions of forskolin (0.01-0.03 micromol 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. Nimodipine, a L-type calcium channel blocker, antagonized the increases in exhaled NO in response to prenalterol infusions. The increases in exhaled NO in response to adrenaline and prenalterol were also present in blood-free, buffer perfused lungs during constant-flow conditions. 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.
Adding
L C
LC
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Agvald
P
P
Artlich
A
A
Persson
M G
MG
Gustafsson
L E
LE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D011294:Prenalterol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D011294:Prenalterol; D013726:Terbutaline; D004837:Epinephrine