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Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats

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Summary

In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K+-induced45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal antihypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the antihypertensive effect of verapamil and related calcium channel blockers.

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Authors and Affiliations

  1. E.I. du Pont de Nemours and Company (Inc.), Experimental Station, 400/5412, 19898, Wilmington, Deleware

    Martin J. M. C. Thoolen, Cathy R. Miller, Andrew T. Chiu & Pieter B. M. W. M. Timmermans

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  1. Martin J. M. C. Thoolen
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  2. Cathy R. Miller
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  3. Andrew T. Chiu
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  4. Pieter B. M. W. M. Timmermans
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Thoolen, M.J.M.C., Miller, C.R., Chiu, A.T. et al. Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats. Cardiovasc Drug Ther 1, 377–383 (1987). https://doi.org/10.1007/BF02209079

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