15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and phenyl-biguanide

Injections of the thromboxane A(2) mimetic U-46619 (10 and 20 microg) into the left atrium of anesthetized rabbits evoked decreases in heart rate (HR) and arterial blood pressure (ABP) followed by an increase in ABP. Bilateral, cervical vagotomy abolished the U-46619-induced bradycardia and attenuated the hypotension. Injections of U-46619 into the ascending aorta did not evoke the bradycardia and hypotension but did cause arterial hypertension. To further define the origin of the vagal reflex, recordings of nerve impulses were made from 11 chemosensitive cardiac vagal afferent nerves. Impulse frequency increased in all 11 fibers in response to left atrial injections of phenylbiguanide (20-30 microg) and U-46619 (5-10 microg). Onset time of nerve activity induced by U-46619 correlated with the onset time of bradycardia. We conclude that U-46619 injections into the left heart elicit decreases in HR and ABP via a vagal reflex that originates from the heart similar to the coronary chemoreflex described for other agents.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Anesthesia; Animals; Biguanides; Blood Pressure; Bradycardia; Chemoreceptor Cells; Female; Heart Atria; Heart Rate; Hypertension; Hypotension; Male; Neurons, Afferent; Rabbits; Reflex; Serotonin Receptor Agonists; Thromboxane A2; Vagotomy; Vagus Nerve; Vasoconstrictor Agents

The purpose of the present study was to determine the influence of NG-nitro-L-arginine methyl ester (L-NAME) on pulmonary vascular responses to endothelium-dependent relaxing factor- (EDRF) dependent and EDRF-independent substances in the pulmonary vascular bed of the anesthetized cat. Because pulmonary blood flow and left atrial pressure were kept constant, changes in lobar arterial pressure directly reflect changes in pulmonary vascular resistance. When pulmonary vasomotor tone was actively increased by intralobar infusion of U-46619, intralobar bolus injections of acetylcholine, bradykinin, serotonin, and 5-carboxyamidotryptamine (a serotonin1A receptor agonist) decreased lobar arterial pressure in a dose-related manner. The pulmonary vasodilator response to serotonin, but not to 5-carboxyamidotryptamine, acetylcholine, and bradykinin, was significantly decreased by L-NAME (100 mg/kg i.v.). Administration of ritanserin (0.5 mg/kg i.v.), but not L-arginine (1 g/kg i.v. with 60 mg.kg-1 x min-1 i.v. infusion), reversed the inhibitory effects of L-NAME on the pulmonary vasodilator response to serotonin and abolished the enhanced pulmonary vasoconstrictor response to (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminoproprane hydrochloride (a serotonin2 receptor agonist) after L-NAME administration. In conclusion, the present experiments suggest that L-NAME inhibits the pulmonary vasodilator response to serotonin by increasing the sensitivity of serotonin2 receptor-mediated vasoconstriction and not by inhibiting EDRF formation. Because the pulmonary vasodilator responses to bolus administration of acetylcholine and bradykinin were not inhibited by L-NAME, these data suggest that L-NAME does not appear to be an adequate probe to study the role of endogenous EDRF in the adult feline pulmonary vascular bed in vivo.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Amphetamines; Animals; Arginine; Biguanides; Cats; Hypoglycemic Agents; Isoproterenol; NG-Nitroarginine Methyl Ester; Nitric Oxide; Prostaglandin Endoperoxides, Synthetic; Pulmonary Circulation; Serotonin; Serotonin Receptor Agonists; Vasoconstriction; Vasoconstrictor Agents; Vasodilation