Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Abstract

Tbe mechanisms mediating the etl'ects ofthyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricolar (i.c. v.) injection of TRH (8 pmol-80 nmollkg) induced dose-dependent lncreases in mean arterial pressure, heart rate, and cardiac index. Rindquarter blood Oow increased due to vasodilation, while an lncrease in renal and mesenteric vascular resistance caused a decrease in blood Oow in the respective organs. The plasma Ievels of norepinephrine a~d epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. Tbe cardiovascular actions of i.c. v. TRH were not in.fluenced by blockade of the renin-angiotensin system or vasopressin receptors. Tbe ganglion blocker chlorisondamine and the a 1 -aod al-adrenoreceptor antagooist phentolamlne (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c. v. TRH. Propranolol (2 mg/kg i. v.) blocked the TRH-ioduced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodllatlon lnduced by TRH was also blocked by the selective ß 1 -adrenocept9r antagonist ICI 188,551(1 or 2 mg/kg i.v.), while tbe ,8,-adrenoceptor blocker practolol (10 mg/kg i.v.) had no eft'ect on the hindquarter vasodiJation produced by TRH but totally blocked the increase in cardiac Index. In adrenal demedullated rats, the systemic hemodynamic eft'ects ofi.c. v. TRH were dimlnished along with the decrease in renal blood flow and lncrease in renal vascular resistance; however, the iocrease in hfndquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetlc blocker bretylium. The renal vasoconstriction induced by i.c. v. TRH was not abolished by renal denervation. In sinoaortic debufl'ered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data soggest that the putative rieurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both tbe sympathetic nerves and the adrenal medulla. A pivotal roJe for ß 1 -adrenoceptors in mediation ofhindquarter vasodilation ls also demonstrated. (Circulatlon Research 1988;62:139-154) T . hyrotropin·releasing hormone (TRH, L·pyro-glutamyl·L-histidyl-L·prolinamide) was the first hypothalamic releasing factor to be isolated, chemically characterized, and synthesized (for review, see Prasad 1 ). In addition to its endocrine actions (thyrotropin, prolactin, and growth hormone release), TRH elicits multiple autonomic effects (e.g., arousal, analeptic effect, increased locomotor activity, and changes in body temperature, respiration, blood pressure, and heart rate) that are unrelated to its action on the hypothalamic pituitary axis (for review, see Horita et al,2 Griffiths, 3 and Prasad'). Thus, cardiorespiratory responses to intracerebroventricularly (i.c. v.) administered TRH have been reported in hypophys...

Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat

“…Grüfiths et al (24) reported an activation of the metabolic rate of brown adipose tissue of rats which was presumably mediated by a Stimulation of sympathetic nerve activity (5). Moreover, the Stimulation of LA by TRH as previously shown by Andrews and Sahgal (7) may constitute an indirect mode of metabolic activation due to an increased peripheral energy consumption.…”

“…Moreover, high affinity TRH receptors have been localized in various CNS sites ( 4) suggesting that TRH may participate in the mediation or modulation of a variety of CNS functions under physiological conditions. This hypothesis is further validated by the profound effects of TRH on behavioral and autonomic functions after central and peripheral administration in experimental animals ( 5,6,7). In addition to its potent cardiovascular effects, including increases in arterial pressure and heart rate (5), TRH has been shown to increase ventilation in the anesthestized rat after intracerebroventricular (icv) application (6) or after microinjection into various brainstem structures (8).…”

Cardiovascular effects of anatoxin-A in the conscious rat

“…A cable connecting the blood flow receptacle and the Doppler flowmeter (University of lowa, Bioengineering Facility, Model 545C-4) was attached to the animaland the mean blood flow continuously recorded on the physiograph. Vascular resistance was calculated by dividing the mean arterial pressure by blood velocity (Doppler shift in kilohertz) as earlier described (Haywood et a/.. 1981;Siren et al. 1988;Siren and Feuerstein, 1986).…”

Effects of NG‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone

“…TRH has been found to influence several important physiological functions including those of the autonomic nervous system (Feuerstein et al, 1983;Koskinen, 1986a;Seligsohn & Koskinen, 1991). Complex effects on the cardiovascular system have been demonstrated (Feuerstein et al, 1983;Siren et al, 1988). In the rabbit, TRH has been found to elicit cerebral vasodilatation by activation of an intrinsic cerebral vasodilating neural pathway (Koskinen, 1986a) which involves a yohimbinesensitive mechanism (Seligsohn & Koskinen, 1991).…”