The effect of intrahypothalamic injection of homodimaprit on blood pressure.
Bilateral injection of the inhibitor of histamine-N-methyltransferase, SKF 91488, which is also known as homodimaprit (5 micrograms), into the preoptic area of the rat produced delayed hypertension, tachycardia and hyperthermia. Some animals exhibited pulmonary edema. These effects were only noted 18-24 hr after an injection and were not an artifact of the injection, since the administration of artificial cerebrospinal fluid produced none of these effects. At the time noted, lesions of the rostral hypothalamus, including the preoptic area, were evident. Injection of a vasopressin antagonist, intravenously, did not lower the blood pressure of the hypertensive animals nor did previous bilateral adrenal demullation prevent or delay the hypertension or tachycardia. Therefore, it does not appear that hypersecretion of either vasopressin or adrenal catecholamines contributed to the cardiovascular effects. Peripheral pretreatment with the sympathetic neurotoxin 6-hydroxydopamine however, did prevent the delayed rise in blood pressure following an injection of homodimaprit. From these studies, it is concluded that the injection of homodimaprit produces lesions in the preoptic area, resulting in hypertension that is maintained by excessive activation of the sympathetic nervous system.
D000313:Adrenal Medulla / Q000601:surgery; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000502:physiology; D017259:Dimaprit / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D011654:Pulmonary Edema / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical; D013890:Thiourea / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D001127:Arginine Vasopressin; C024535:SK&F 91488; D008780:Methyltransferases; D006637:Histamine N-Methyltransferase; D013890:Thiourea; D017259:Dimaprit