Thyrotropin-releasing hormone receptor activation in the spinal cord increases blood pressure and sympathetic tone to the vasculature and the adrenals.
Cardiovascular and regional hemodynamic effects of the intrathecal (i.t.) administration of a thyrotropin-releasing hormone (TRH) analog, MK-771 (L-pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide), were studied in rats. MK-771 (0.01-5.0 micrograms i.t.) caused dose-related increases in mean arterial pressure (MAP) and heart rate (HR). TRH (10 micrograms i.t.), but not TRH-free acid, produced similar cardiovascular effects. The MAP response to MK-771 (i.t.) remained primarily intact after cervical spinal cord transection, whereas the HR response was attenuated (37% of control). The MAP response to MK-771 was blocked by peripheral administration of pentolinium or phentolamine, and was partially attenuated by adrenalectomy. The HR response was reduced by pentolinium or atropine. Assessment of changes in regional blood flow and vascular resistance with the radioactive microsphere technique showed that MK-771 increased total peripheral resistance and vasoconstricted cutaneous, skeletal muscle, adrenal, renal and intestinal vascular beds. Cardiac output and stroke volume were not altered. MK-771 had no effect on vascular resistance locally or in other central nervous system structures. However, blood flow was elevated by MK-771 in spinal cord and brain. These data show that TRH receptor activation in the thoracic spinal cord, presumably in the intermediolateral cell column, elevated MAP by increased sympathetic activity to the peripheral vasculature and the adrenals. However, the HR response to TRH receptor activation required a supra-spinal component and was mediated in part by vagal inhibition.
Helke
C J
CJ
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Phillips
E T
ET
D000311:Adrenal Glands / Q000187:drug effects / Q000294:innervation*; D000315:Adrenalectomy; D000818:Animals; D001340:Autonomic Nerve Block; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D012039:Regional Blood Flow; D013116:Spinal Cord / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide