Vagal blockade does not prevent adrenocorticotropin, cortisol, and cardiopulmonary responses to thromboxane A2

Previously, we reported that thromboxane A2 (TxA2) mediates heart rate, adrenocorticotropin (ACTH), cortisol, and blood gas responses, although the specific site of action was not identified. In the present study, we interrupted vagal nervous transmission in chronically instrumented conscious sheep and infused the TxA2 mimetic U46619 or saline into the carotid artery or U46619 into the vena cava to determine whether TxA2 acts at vagal afferent nerves. Heart rate increased in all three groups during vagal blockade, and responses were not different between groups. Carotid artery and intravenous infusions of U46619 resulted in an increase in blood pressure, but responses were not different between groups. PaO2 decreased in response to vagal blockade in all groups, and responses were not different among groups. Arterial pH increased and PaCO2 decreased during vagal blockade in response to carotid artery U46619 infusions but not in response to vagal blockade alone or combined with carotid artery saline or intravenous U46619. ACTH, cortisol, and hematocrit increased significantly in response to carotid artery infusions of U46619 during vagal blockade but not in response to carotid artery saline or intravenous U46619 infusions. In summary, carotid artery infusions of TxA2 mimetic result in ACTH, cortisol, PaCO2, pHa, and hematocrit responses that are not prevented by vagal blockade. We conclude that these responses are mediated at a site perfused by the carotid vasculature and not at a site innervated by the vagal nerves, findings consistent with the hypothesis that TxA2 acts on the brain to mediate cardiopulmonary and pituitary-adrenal responses.Key words: thromboxane A2, vagus, U46619, adrenocorticotropin, cortisol, prostaglandins, blood pressure, heart rate.

Intracerebral adrenoceptor agonists influence rat duodenal mucosal bicarbonate secretion

We have studied the effects of intracerebral administration of selective alpha-adrenergic agonists on duodenal bicarbonate secretion. Duodenum free of Brunner's glands was cannulated in situ in anesthetized rats, and bicarbonate secretion into the luminal reperfusate was continuously titrated by pH stat. Infusion of the alpha 1-selective adrenoceptor agonist, phenylephrine (1,000–2,500 micrograms.kg-1.h-1), into a lateral brain ventricle increased (P< 0.01) duodenal bicarbonate secretion. Pretreatment with prazosin, an alpha 1-antagonist, significantly (P< 0.01) reduced the stimulatory effect when infused into the lateral ventricle (30 micrograms.kg-1.h-1), but not when administered intravenously (1,000 micrograms.kg-1.h-1). Hexamethonium (10 mg.kg-1.h-1 iv) abolished stimulation, whereas cervical vagotomy, epidural blockade, and naloxone were each without effect. Vasopressin, vasopressin antagonists, ts, and oxytocin did not affect basal secretion. Intracerebro-ventricular administration of the alpha 2-adrenoceptor agonist, clonidine (1,000 micrograms.kg-1.h-1), in contrast to alpha 1-receptor activation, decreased (P< 0.01) the secretion. Thus central nervous adrenoceptors influence duodenal mucosal bicarbonate te secretion, and alpha 1-adrenoceptor stimulation may provide protection against luminal acid. This potent stimulation was not mediated by the vagal nerves, spinal cord pathways, or the release of beta-endorphin but involves nicotinic, possibly enteric nervous transmission.

Effect of Ingestion of Smokeless Tobacco on Motor Distal Latency of the Median Nerve

Subjects were 17 men between the ages of 18 and 32 yr. and regular users of smokeless tobacco. Each subject received three treatments consisting of one pouch of Skoal Bandits, one pinch of their regular brand, and a nonnicotine piece of chewing gum. The nervous transmission at the neuromuscular junction in the right thumb was compared before treatment and once every minute for 15 min. after treatment. Repeated-measures analysis of variance indicated a significant increase in the distal latencies for both the brand-name grouping and in the regularly used brand. No such difference was found in a control group when compared to the pretest results. It was concluded that smokeless tobacco ingestion resulted in a delay in the nervous transmission across the neuromuscular junction. This delay was hypothesized to be caused by the enduring binding action of nicotine to the acetylcholine receptor sites, thereby blocking the impulse in some of the faster conducting nerve fibers.