Failure of verapamil and diltiazem to attenuate the pressor response to hypothalamic stimulation: a possible mechanism.
The effects of verapamil or diltiazem on pressor responses to posterior hypothalamic stimulation, injected noradrenaline or tyramine were studied in urethane-anaesthetized normotensive, deoxycorticosterone acetate (DOCA), renal and spontaneously hypertensive rats at the early and established phases of hypertension. Pressor responses to the pressor stimuli were significantly enhanced in the early and established phases of hypertension when compared with the normotensives. While the magnitude of pressor responses in the established phase of renal or spontaneously hypertensive rats was significantly higher (P less than 0.05) than the corresponding value in the early phase, in contrast, the pressor response in the early phase of DOCA hypertension was significantly higher than that of the established phase. Verapamil or diltiazem significantly (P less than 0.005) inhibited pressor responses to injected noradrenaline or tyramine in all groups of rats but not that to hypothalamic stimulation, irrespective of the stage of hypertension. When the probable mechanism of the hypothalamic pressor response's resistance to the calcium antagonists was studied in-vitro, ATP significantly (P less than 0.005) inhibited the relaxant effect of the calcium antagonists in the rat aortic strips. Our data indicate that verapamil or diltiazem is ineffective in inhibiting the pressor response to posterior hypothalamic stimulation. The probable mechanism of the resistance and the clinical implication of the findings are discussed.
Department of Pharmacology and Toxicology, University of Benin, Nigeria.
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AE
Eferakeya
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UA
Osunkwo
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D004110:Diltiazem / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology; D007034:Hypothalamus, Posterior / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014439:Tyramine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D003900:Desoxycorticosterone; D014700:Verapamil; D004110:Diltiazem; D009638:Norepinephrine; D014439:Tyramine