The cardiovascular effects of thyrotropin-releasing hormone (TRH) are attenuated by cimetidine in rats.
The modulation of cardioventilator effects of thyrotropin-releasing hormone (TRH) by histaminergic mechanisms was studied in anaesthetized rats pretreated with histamine receptor antagonists. TRH (1-100 nmol/kg) into the lateral cerebral ventricle dose-dependently elevated mean arterial pressure, heart rate and stimulated respiration. The respiratory stimulating effect of TRH remained unchanged after pretreatments with histamine H1-receptor antagonist diphenhydramine or H2-receptor antagonists cimetidine and ranitidine, while the TRH-induced hypertension and tachycardia were attenuated by cimetidine. This antagonism was not due to an interaction between TRH and cimetidine at their central binding sites, since there was no displacement of [3H]MeTRH binding in the presence of cimetidine nor did TRH displace [3H]cimetidine in rat brain homogenates. Inability of diphenhydramine to modify the cardiovascular effects of TRH indicates that these effects are not due to histamine liberation, as cardiovascular stimulation after central administration of histamine is mainly mediated via H1-receptors. The antagonism of the cardiovascular responses to TRH by cimetidine was not due to blockade of H2-receptors, since another potent H2-receptor antagonist ranitidine was unable to affect the cardiovascular effects of TRH. Therefore, we suggest that cimetidine exerted antagonism of TRH by some non-specific action.
Nurminen
M L
ML
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Paakkari
I
I
Jrvinen
A
A
Vonhof
S
S
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism; D008297:Male; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; D002927:Cimetidine; D006632:Histamine; D011899:Ranitidine; D004155:Diphenhydramine