Cardiovascular pharmacology of thyrotropin releasing hormone

Abstract

SIREN A.-L. Cardiovascu/ar pharmacology of thyrotropin releasing hormone. PEPTIDES 9: Suppt. l, [69][70][71][72][73] 1988.-Thyrot;opin releasing hormone (TRH) and its receptors are present in th~ car~iovascul~ nuclei ofthe brain as ~ell as in ~he intermediolateral cell column of spinal cord. Anatomical, neurophysiological, funchonal and pharmacological stud1es suggest that TRH is a neurotransmitter/neuromodulator in the centrat nervous system. Administration of TRH to experimental animals or human subjects induces pressor and tachycardic responses and increases plasma Ievels of catecholamines. These effects are likely tobe mediated by a central nervous system activation of the sympathoadrenomedullary system with no involvement of vasopressin or renin-angiotensm system. ln the conscious rat, the TR~-induced pressor response is accompanied by an increment in cardiac output and a distinct change in organ blood flow, a hmdquarter skeletal muscle vasodilation accompanied bv renal and mesenteric vasoconstriction. The rote ofTRH in hypertension has not been studied. However, the extremely potent pressor and vasoconstrictor properties of TRH makes this tripeptide a candidate for neurotransmitters/modulators involved in the development and/or maintenance ofhypertension. The role ofTRH in the therapy of shock is at present controversial. Though preliminary experimental work raised hopes and expectations for therapeutic usage of TRH in shock and trauma, the more recent studies have shown no effect or a detrimental effect for TRH in some experimental shock states. TRHBlood pressure Organ blood flow Sympathetic nerve activity THYROTROPIN releasing hormone (TRH, 1-pyroglutamyl-1-histidyl-1-prolinamide) was the first hypothalamic releasing factor to be isolated, chemically characterized and synthesized [43]. In addition to its neuroendocrine effects (TSH, prolactin, growth hormone release), this tripeptide has centrat nervous actions which are totally unrelated to its effect on the hypothalamopituitary axis (for review see [29,38]). The presence of TRH immunoreactivity and TRH receptors in brain areas related to the cardiorespiratory control, together with the extremely potent pressor and tachycardic actions of exogenously administered TRH suggest that this peptide might have a role in modulating the brain regulation of blood pressure and respiration. This review aims to summarize the sturlies on TRH in the centrat nervous system with special emphasis on the cardiovascular pharmacology of this peptide. TRH SYSTEM IN THE DRAINTRH immunoreactivity is unevenly distributed throughout the centrat nervous system (see [42,43]). Although the highest local concentrations are found in the hypothalamus (especially in the median eminence, periventricuJar arcuate, dorsomedial and ventromedial nuclei), more than 70% of the total CNS TRH is located in extrahypothalamic areas. Outside the hypothalamus high locallevels of TRH are found in the lateral nucleus of the septum in the limbic area and in the nucleus of the solitary tract (NTS) in the...

The effects of calcium channel blocker and thyrotropin releasing hormone on acute necrotizing pancreatitis in rats

“…Thyroid-releasing hormone (TRH) as an opiate antagonist alone has no effect on the course of acute experimental pancreatitis [1,10], but it improves cardiovascular performance as well as survival in hemorrhagic and endotoxic shock [20].…”