The Central Vasomotor Effects of 5‐hydroxytryptamine

Abstract

In the dog, injection of 5-hydroxytryptamine into the cerebral ventricles caused hypotension, inhibition of the pressor response to occlusion of the carotid artery and inhibition of the pressor or depressor response evoked by electrical stimulation of the central end of the cut vagus. Hypotension and inhibition of the vagal vasomotor response also occurred in dogs in which the carotid sinuses had been denervated and the vagi cut. The site of action was central. Local cerebral vascular changes could not have been responsible for the action. The central vasomotor effects of 5-hydroxytryptamine are mediated through the sympathetic outflow. Implications of these findings are discussed in relation to the effects of intravenous 5-hydroxytryptamine and the mechanism of action of reserpine.Feldberg and Sherwood (1954) studied the effects of drugs introduced into the ventricular system of cats through an implanted metallic cannula. Using a simple polyethylene cannula for injecting drugs into the lateral cerebral ventricles of dogs, we have studied the central vasomotor effects of 5-hydroxytryptamine in this species.It is generally believed that the quantity of 5-hydroxytryptamine which penetrates the bloodbrain barrier after parenteral administration is too small to produce central effects. However, a measurable rise of brain 5-hydroxytryptamine occurs on parenteral administration into mice (Shore, Pletscher, Tomich, Carlsson, Kuntzman, and Brodie, 1957). In this species an intraperitoneal injection of 5-hydroxytryptamine produces, like reserpine, general depression of muscular activity, sedation, and potentiation of the hypnotic action of barbiturates and ethanol (Shore, Silver, and Brodie, 1955). A direct inhibition of central synaptic transmission was observed by Marrazzi and Hart (1955) after the intracarotid injection of small doses of 5-hydroxytryptamine into cats, and Malcolm (1958) showed that intracarotid injection of 5-hydroxytryptamine into cats depressed the cortical response evoked by sensory nerve stimulation, but only with large doses. There are a few observations which show that 5-hydroxytryptamine, by a central action, can influence blood pressure and its responses. Bhargava and Borison (1957) found that, in cats, pressor responses elicited by threshold electrical stimulation of the medulla oblongata were depressed by large doses of 5-hydroxytryptamine given intravenously. The effect was similar to that after reserpine. Costa and Aprison (1957) observed in cross-circulation experiments that perfusion of the isolated head with 5-hydroxytryptamine caused a fall of arterial blood pressure in the recipient. A central depressor action of 5-hydroxytryptamine had previously been suggested by Ginzel and Kottegoda (1954) to explain the depressor effect obtained on its injection into the subclavian artery.The present experiments show that 5-hydroxytryptamine injected into the cerebral ventricles of dogs caused a fall in arterial blood pressure, probably due to inhibition of sympathetic vasoconstrictor tone

Central Mechanism of Vasopressin‐induced Changes in Antidiuretic Hormone Release

“…Two or three hours after the surgical procedure, when the urine flow rate was constant over a period of 30 min, the drugs were administered through a cannula implanted in one of the lateral cerebral ventricles (Bhargava & Tangri, 1959 (Innes & Nickerson, 1970). In a previous study, intracerebroventricular injection of histamine was shown to induce an antidiuretic response which has been attributed to a massive release of catecholamines (Bhargava et al, 1973).…”

Role of catecholamines in centrogenic cardiac arrhythmia induced by aconitine

“…Intracerebroventricular (i.c.v. ) injections of aconitine were made through a stainless steel cannula introduced into the lateral ventricle according to the method descrilbed by Bhargava & Tangri (1959). Aspiration of cerebrospinal fluid indicated the proper placement of the cannula, which was confirmed at necropsy.…”

Antagonism of Central Vasomotor Effects of Lysergic Acid Diethylamide (Lsd-25) by Morphine

“…The left common carotid artery was cannulated to record the blood pres sure with a mercury manometer on smoked paper. The drugs were administered in the left lateral cerebral ventricle (intraventricularly) through a polythene cannula implanted according to the technique of Bhargava and Tangri (6). The drugs were administered dissolved in 0.25 ml distilled water (lysergic acid diethylamide tartrate) or normal saline (morphine hydrochloride) followed by same volume of the blank fluid.…”