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Cardiovascular effects of cromakalim (BRL 34915) in healthy volunteers
J S Fox1, E M Whitehead, R G Shanks
1Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Abstract:
1. The effect of oral doses of cromakalim 0.5, 1.0, 1.5 and 2.0 mg on several cardiovascular parameters was studied in healthy male volunteers. 2. In the first study, no dose of cromakalim reduced systolic or diastolic blood pressure in the supine or standing position. Reductions of diastolic blood pressure after exercise (P less than 0.01) were observed 4 h after administration of 2.0 mg. 3. There was a trend towards increased heart rate after 2.0 mg at all time intervals, and significant changes were observed in supine and standing heart rate at 2 and 4 h (P less than 0.01). No significant change was observed in exercise heart rate. 4. In the second study small increases in forearm blood flow were observed from 3 h to 5 h after oral administration of 1.0 and 2.0 mg of cromakalim. Forearm vascular resistance was significantly reduced after 2.0 mg (P less than 0.025) when compared with placebo. No change was observed in forearm venous capacitance after either dose of cromakalim, or placebo. Supine heart rate was significantly increased 4 h after 2.0 mg of cromakalim (P less than 0.025). 5. These results show that oral administration of cromakalim decreases diastolic blood pressure and forearm vascular resistance. A hypotensive effect is probably attenuated by reflex tachycardia.
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