Pharmacological study of a cholinergic mechanism within the rat posterior hypothalamic nucleus which mediates a hypertensive response

Neurophysiology and neuropharmacology of cardiovascular regulation and stress

Regulation of blood pressure by central neurotransmitters and neuropeptides.

The third ventricle and the aqueduct of anaesthetized cats were cannulated and the posterior area of the hypothalamus was stimulated with a monopolar electrode. Electrical stimulation of the posterior area evoked a rise of the arterial blood pressure which was inhibited by the injection of 0.2 ml of gammaaminobutyric acid (GABA, 2M) into the third ventricle. The impairment of the pressor response to electrical stimulation was accompanied by a fall of the “resting” blood pressure and depression of the respiration, presumably by action of GABA on brain areas in the vicinity of the fourth ventricle. In another series of experiments the posterior area was labelled with (±)-3H-noradrenaline and 2 h later superfused with a push-pull cannula and stimulated with the tip of the cannula. Superfusion with GABA (0.1 or 1 M) evoked a dose-dependent increase of release of catecholamines and enhanced the pressor response to electrical stimulation. 1×10−3 M of GABA enhanced the pressor response without increasing the spontaneous release of catecholamines but potentiated the output of radioactivity during electrical stimulation. Superfusion with sucrose (1 M) did not influence either pressor response or release of radioactive compounds. Superfusion with GABA increased slightly but significantly the relative concentration of catechols in the effluents and reduced that of normetanephrine. Pretreatment of animals with pargyline and tropolone evoked a pronounced increase of the relative concentrations of catechols in the effluent, while those of 3-methoxy-4-hydroxyphenylglycol and 3-methoxy-4-hydroxymandelic acid were strongly reduced. It is concluded that superfusion with high concentrations of GABA enhances the pressor response by increasing the release of catecholamines, while the effect of low GABA concentrations is due to facilitation of release of catecholamines from the adrenergic nerve endings during electrical stimulation.

Superfusion of the hypothalamus with gamma-aminobutyric acid. Effect on release of noradrenaline and blood pressure.

Electrical stimulation of the locus coeruleus or of the hypothalamic posterior area of cats under pentobarbitone anaesthesia elicited a rise of the arterial blood pressure. Electrocoagulation of the hypothalamic posterior area or its lesion by the injection of ethanol significantly diminished the pressor response to electrical stimulation of the locus coeruleus. The pressor response to electrical stimulation of the area posterior was almost completely abolished after electro-coagulation and strongly inhibited after injection of ethanol. It is suggested that adrenergic neurones ascending from the locus coeruleus to the posterior hypothalamus may be involved in the hypothalamic regulation of the arterial blood pressure.

Reduced pressor responses to stimulation of the locus coeruleus after lesion of the posterior hypothalamus.

The third ventricle and the aqueduct of the anaesthetized cat were cannulated and the hypothalamus was superfused with artificial cerebrospinal fluid. Electrical stimulation of the nucleus posterior of the hypothalamus elicited a rise of the blood pressure of 58±3 mm Hg (n=20). Superfusion of the hypothalamus with artificial cerebrospinal fluid containing bretylium (5×10−3 M) caused a gradual and long lasting impairment of the rise of blood pressure due to stimulation of the nucleus posterior. Tetracaine (1×10−3 M) diminished the rise of blood pressure to about the same extent as did 5×10−3M of bretylium; the inhibitory action of tetracaine was completely reversed within 120 min. Pretreatment of cats with 6-hydroxydopamine, which was applied through a Collison cannula implanted into the lateral ventricle, evoked a decrease of the noradrenaline content of the hypothalamus and of the rest of the brain and an impairment of the rise of blood pressure during stimulation of the nucleus posterior (33±3 mm Hg;n=6). The blood pressure of the anaesthetized cats was not affected by pretreatment with 6-hydroxydopamine. Superfusion of the hypothalamus with desipramine (1×10−4M) enhanced the rise of blood pressure elicited by electrical stimulation. The results are compatible with the assumption that the rise of blood pressure during stimulation of the nucleus posterior of the hypothalamus is mediated by adrenergic neurons of the brain.

A. Philippu

Papers

Importance of adrenergic neurons of the brain for the rise of blood pressure evoked by hypothalamic stimulation.