Sympathomimetic pressor responses to thyrotropin-releasing hormone in rats

Abstract

Cardiovascular responses to centrally administered thyrotropin-releasing hormone (TRH) were studied in urethan-anesthetized rats to allow continuous recording of attendant changes in sympathetic nerve activity. Intracerebroventricular infusions of TRH (0.05-5.0 micrograms) consistently increased not only blood pressure and heart rate, but also spike frequency in splanchnic, renal, or cervical sympathetic nerves. Parasympathetic inhibition seemed unlikely because TRH responses were unaltered by cholinergic blockade with atropine, and efferent vagal nerve firing, instead of being reduced, was actually increased by TRH. An increased secretion of endogenous vasopressin also appeared unlikely, since TRH responses were essentially unaffected by either hypophysectomy or pretreatment with a vasopressin antagonist. Inasmuch as pharmacological ganglion blockade with pentolinium eliminated increases in splanchnic nerve firing but reduced the attendant tachycardia by only 50%, residual tachycardia after ganglion blockade was considered partly due to persistent sympathetic cardioaccelerator tone. On the other hand, because pressor responses to TRH were always accompanied by increased sympathetic nerve firing and were completely abolished after pentolinium-induced ganglioplegia, they were attributed solely to sympathetic hyperactivity.

Hemodynamic defense response to thyrotropin-releasing hormone injected into medial preoptic nucleus in rats

“…Indeed, when efferent sympathetic nerve activity was directly monitared in the anesthetized rat, TRH increased sympathetic outflow by 200%, even at a dose (2.4 pmol) that had no significant hemodynamic effects in the anesthetized rat. Again, our present data were weil in agreement with the previous sturlies in which icv TRH produced elevations in the circulating Ievels of catecholamines (26) and increased efferent sympathetic nerve activity in the renal and splanchnic sympathetic nerves (16,17). Furthermore, the hemodynamic responses to icv TRH were also effectively blocked by ganglionic blockers, adrenolytic drugs, and adrenergic antagonists (16,17,26), whereas hypophysectomy, thyroidectomy, or treatment with arginine vasopressin or angiotensin antagonists did not abolish the TRH responses (3,16,17,26).…”

“…Pressor and tachycardic responses were also reported after icv infusion of TRH at picomole doses in halothane-anesthetized rats (5), whereas, in the urethane-anesthetized rat, significant increments in blood pressure were seen only after nanomole doses of TRH, and the onset of the TRH effects in the urethane-anesthetized rat was significantly slower; the maximum responses were observed 15 min after the administration of TRH and were sustained for 30 min (16,17). Interestingly, similar sustained pressor responses with slow onset were recently reported after injections of nanomale doses of TRH into the dorsal raphe nucleus (18).…”

Thyrotropin-Releasing Hormone Decreases Leptin and Mediates the Leptin-Induced Pressor Effect

“…9 This effect was blocked by the destruction of the sympathetic system, indicating that the pressor effect could be mediated by catecholamines involving the modulations of diverse neurotransmitter system activities. 16 Leptin gene expression and secretion are nutritionally as well as hormonally regulated; they are increased by overfeeding, high-fat diet, insulin, and glucocorticoids, and they are decreased by fasting and cathecolamines. 17,18 Therefore, it is tempting to speculate with regard to whether a reciprocal interaction exists between periventricular TRH and leptin levels mediated by the sympathetic outflow.…”

Cardiovascular pharmacology of thyrotropin releasing hormone

“…Studies in progress in our laboratory have shown that in the conscious rat systemic administration of a high dose of TRH (2 mg/kg) induced a statistically significant rise in plasma vasopressin, but the magnitude of this increase was below the Ievels at which vasopressin can induce changes in blood pressure (7]. Pretreatment of urethane-anesthetized rats with a vasopressin antagonist failed to block the cardiovascular actions of ICV administered TRH [37]. The involvement of the other pressor system, the renin-angiotensin system, in the hypertensive effect of TRH seems also likely, since TRH has no effect on plasma renin activity in either the conscious rat (own unpublished observations) or in man [39].…”