The relationship between calcium antagonist-induced hypotension and central monoaminergic system in spontaneously hypertensive rats.
Central monoamines (MA) are believed to have an important role in regulating the blood pressure and the antihypertensive effect of calcium antagonists cannot be explained only by the reduction of the increased peripheral vascular resistance. In the present studies various doses of nitrendipine which is a new derivative of nifedipine were compared for their potencies to affect the blood pressure and heart rate, as well as the effect of drug-induced hypotension at the monoamine level in the spontaneously hypertensive rat (SHR) brain areas. Comparative studies were carried out through fluorescent histochemical observations of the SHR brain, adrenal gland and femoral artery. In the conscious animals nitrendipine-induced hypotension was significant after the administration of doses of 10, 20 and 30 mg/kg but not at 1 mg/kg administered to SHRs, although there is a significant increase of the heart rate in the 20- and 30-mg/kg administered groups. Drug-induced hypotension was accompanied by increasing monoamines levels and a reduction in the levels of their metabolites. The alteration is dose-dependent and seems to induce an apparent change in the catecholaminergic system. Fluorescent histochemical studies showed that this drug increased the intensity of noradrenaline fluorescence in the median eminence and adrenal medulla, and decreased that in the outer layer of femoral artery. In conclusion, calcium antagonist-induced hypotension in SHRs might be associated with change in the central monoamine level as the drug-induced decrease of monoamine turnover.
Department of Pharmacology, Tokyo Medical College, Japan.
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Hong
D000313:Adrenal Medulla / Q000032:analysis / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D004298:Dopamine / Q000032:analysis; D005263:Femoral Artery / Q000032:analysis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006651:Histocytochemistry; D006973:Hypertension / Q000188:drug therapy; D007022:Hypotension / Q000139:chemically induced*; D009568:Nitrendipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000032:analysis*; D051381:Rats; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000032:analysis
D012701:Serotonin; D009568:Nitrendipine; D004298:Dopamine; D009638:Norepinephrine