Comparison of the Acute and Chronic Hemodynamic Effects of Captopril and Guanethidine in Spontaneously Hypertensive Rats

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Abstract
The present study compared the hemodynamic effects of captopril with those of guanethidine as well as with a combination of these two drugs in conscious male spontaneously hypertensive rats. Acutely, captopril or guanethidine or a combination of the two lowered arterial pressure to similar levels. The reduction in pressure with captopril alone or in combination with guanethidine, was due to a lowering of all organ vascular resistances. Guanethidine alone lowered pressure by reducing cardiac output. Chronically, captopril or guanethidine lowered arterial pressure to similar levels by reducing organ vascular resistances to comparable levels, particularly skeletal muscle, skin and splanchnic organs. Combination of these two drugs had an additive effect on the reduction of arterial pressure and organ vascular resistances. Since, chronically, the addition of guanethidine to captopril therapy enhanced rather than attenuated the hemodynamic changes induced by captopril, these drugs are probably acting by different mechanisms and the mechanism of action of captopril does not require an intact sympathetic nervous system.