Adrenergic and non-adrenergic cardiovascular effects of thyrotropin-releasing hormone (TRH) in the anaesthetized rabbit

Abstract

The effects of thyrotropin-releasing hormone (TRH) on regional blood flows were studied in urethane-anaesthetized rabbits. Experiments were performed both with and without adrenergic antagonist pretreatment. The tracer microsphere method was used to measure blood flow. TRH (0.1 mg kg-1) caused an increase in mean arterial blood pressure (MAP) from 9.8 +/- 1 to 11.8 +/- 0.8; a higher dose (1 mg kg-1) increased the blood pressure to 15.2 +/- 1 kPa (P less than 0.001). Total cerebral blood flow (CBFtot) increased to 137 +/- 10% (P less than 0.05) of control at the lower dose and to 214 +/- 16% (P less than 0.001), at the higher dose. A reduction in blood flow at both doses of TRH in several peripheral organs indicates that the pressor effect was mainly due to an effect on the peripheral vascular resistance. In prazosin-pretreated animals in which the MAP was normalized by ligation of the thoracic aorta, TRH elicited an increase in the CBFtot to 131 +/- 12% (P less than 0.05) of control. In the iris, TRH caused vasodilation in prazosin-pretreated animals. In experiments with combined alpha- and beta-adrenergic blockade, a non-adrenergic vasoconstricting effect of TRH was seen in some peripheral organs. The results indicate that TRH activates the sympathetic nervous system thus causing an increased vascular resistance and MAP; these effects are mediated mainly by an alpha 1-adrenergic mechanism. In the spleen, the gastric mucosa and the adrenal glands, the vasoconstriction caused by TRH was partly non-adrenergic. The vasodilation seen in the small intestine and the anterior uvea after TRH treatment and adrenoceptor blockade may be explained by effects on the parasympathetic nervous system. The vasodilating effect of TRH in the brain does not seem to involve alpha 1- or beta-adrenergic mechanisms.