Propranolol and methylatropine antagonize the cardiovascular effects produced by microinjection of the TRH analog MK-771 into the preoptic suprachiasmatic nucleus.
Thyrotropin-releasing hormone (TRH) has been shown to increase heart rate as well as blood pressure when administered into rat brain. The present study investigated the mechanism by which the TRH analog MK-771 produces these effects when injected into the preoptic suprachiasmatic nucleus (POSC). MK-771, at a dose of 125 pmol (50 ng), produced significant increases in both heart rate and blood pressure. These effects occurred within 5 minutes of microinjection and lasted approximately 20-30 minutes. Pretreatment with either the beta-adrenergic antagonist propranolol or the muscarinic antagonist methylatropine, administered into the POSC, significantly altered the response produced by MK-771. Propranolol, at a dose of 7 nmol, and methylatropine at a dose of 0.5 nmol, significantly inhibited the tachycardia produced by MK-771. In addition, methylatropine, at a dose of 0.5 nmol, significantly reduced the increase in diastolic pressure produced by the TRH agonist. These results are consistent with the idea that TRH agonists, when administered centrally, produce cardiovascular alterations through the autonomic nervous system.
Sills
M A
MA
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Jacobowitz
D M
DM
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003971:Diastole / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D010276:Parasympatholytics / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D013599:Systole / Q000187:drug effects; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001286:Atropine Derivatives; D010276:Parasympatholytics; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; C006649:methylatropine; D011433:Propranolol