Alphonse J. Ingenito

Norepinephrine Levels in Various Areas of Rat Brain during Cold Acclimation

Summary Norepinephrine (NE) levels were determined in the hypothalamus, midbrain, and medulla oblongata of rats following exposure to cold of 1°C for 1, 15, and 30 days. In comparison to room temperature controls, hypothalamic levels were slightly increased following 15 and 30 days at 1°C, while levels in the medulla and midbrain were slightly increased only after 30 days of cold-exposure. These increases were unrelated to differences in body temperature, body weight and the water content of brain between cold-exposed and room temperature rats. It is suggested that the increases in brain NE derive from a basis similar to the increases in peripheral tissue catecholamines previously observed by others to follow prolonged cold exposure.

Direct central and reflexly mediated effects of nicotine on the peripheral circulation

Abstract The direct central and some reflexly (chemoreceptor) initiated cardiovascular actions of nicotine were studied using a vascularly isolated, perfused, in-situ cat brain preparation having neural control over the peripheral circulation. 4 different groups were studied relative to the integrity of certain cranial nerves (CN): (a) all CN intact; (b) the carotid branch of CN IX only was sectioned; (c) CN X only was sectioned in the cervical region and (d) CN IX, X, XI and XII were sectioned at the level of the jugular foramina rostral to the nodose ganglia. The effects of perfusion of nicotine hydrochloride through the isolated brain at perfusion blood concentrations of 1 and 10 μg/ml were as follows: In group (a) the effect appeared to depend on concentration, a significant hypotension and bradycardia occurring only at 10 μg/ml. In group (b) the larger concentration caused a marked hypotension and bradycardia. In group (c), 10 μg/ml caused a significant hypertension but little effect on heart rate. At 1 μg/ml, the effect was qualitatively similar but not statistically significant. Finally, in group (d), 10 μg/ml caused a significant hypotension and bradycardia. These results indicate that when nicotine is restricted to blood perfusing only the carotid bifurcation region and the cerebral circulation, the reflex and direct centrallu initiated effects on the peripheral circulation depend to a large extent on the integrity of the afferent and efferent autonomic pathways carried by CN IX and X and possibly to some extent XI and XII. Actions of nicotine contributing to the above effects included activation of carotid chemoreceptors leading to both tachycardia and bradycardia and to both hypertension and hypotension. What appeared to be a direct centrally induced hypotension and bradycardia was also demonstrated. There was no evidence of a direct centrally induced hypertension by nicotine at the above stated blood levels.

An Analysis of the Effects of Nicotine on the Cerebral Circulation of an Isolated, Perfused, in situ Cat Brain Preparation

To determine the effects of nicotine HCl on the cerebral circulation of the cat, without the complicating actions of the drug at other sites in the body, the drug was perfused at concentrations of 1, 10 and 100 μg/ml through a vascularly isolated, perfused in situ cat brain preparation. Cats having selective section of cranial nerves 9, 10, 11 and 12 and the cervical sympathetic trunks comprised various experimental groups. Nicotine was also perfused through an isolated, denervated hindlimb of the same cat for comparative purposes. Nicotine caused only a mild and transient vasoconstriction of the cerebral circulation, mediated primarily by stimulation of the superior cervical ganglia, and a small direct cerebral vasoconstrictor component. An acute tolerance to the cerebral vasoconstrictor effects of repeated increments of nicotine was also observed. The cerebral vasoconstrictor effect of nicotine was diminished in the presence of intact vagi, suggesting a cerebral vasodilator role for these nerves. In contrast, the effect of nicotine on the denervated hindlimb vasculature was a weak but sustained vasodilation. The mechanism of action of nicotine on the cerebral circulation is discussed along with the relevance of these findings to the potential health hazards of tobacco smoking in individuals with cerebrovascular insufficiency.

Some paradoxical aspects of the cardiovascular pharmacology of alpha-methyldopa.

In an effort to help explain why it is often difficult to demonstrate hypotension with alpha-methyldopa on an acute basis in normotensive anesthetized animals, the drug was administered intravenously in single doses of either 50, 100, or 200 mg/kg to chloralose-anesthetized cats while monitoring mean arterial pressure; the systolic pressor response in arterial pressure to bilateral occlusion of the common carotid arteries; hind limb vascular resistance in a vascularly isolated, extracorporeally perfused but neurally intact hind limb; and the response of hind limb vascular resistance to CCO. Alpha-methyldopa failed to cause any significant hypotension and also failed to affect vasomotor tone to the hind limb vasculature, but the drug augmented the pressor response to CCO on MAP and hind limb vascular resistance. Alpha-methyldopa also had no effect on hind limb vascular resistance when added directly to the extracorporeally perfused hind limb vascular resistance when added directly to the extracorporeally perfused hind limb circuit, indicating a lack of direct vascular smooth muscle dilating properties in these preparations. It is postulated that the augmented baroreceptor demonstrated may help th explain why it is difficult to record hypotension on an acute experimental basis with this drug. Such actions of alphamethyldopa might also provide a basis for understanding the development of tolerance to the antihypertensive effects of the drug and instances of paradoxical hypertension with it when these occur in the hypertensive human.