Abstract
The action of the recently developed hypotensive drug ST 155 (Catapres) on the heart and peripheral circulation has been investigated. The intravenous injection of 5 µg/kg of ST 155 into rabbits and dogs caused bradycardia and a biphasic change in arterial blood pressure, characterized by an initial transient pressor response followed by a sustained fall. The initial pressor response was prolonged and often potentiated after pretreatment with either pentolinium tartrate, bnetylium tosylate, reserpine or atropine and after the spinal cord had been transected at C1-2 or C2-3. Both phases of the blood pressure response were modified by phenoxybenzamine. Left ventricular workfunction curves indicated that 5 µg/kg of ST 155 caused a small but significant decrease in left ventricular function during conditions of high, but not under conditions of low, load. It did, however, consistently produce bradycardia. The continuous intravenous infusion of 1.0 µg/kg/min of ST 155 into rabbits resulted in a fall in blood pressure, without any initial pressor response. The similar infusion of ST 155 after reserpine pretreatment resulted in a prolonged pressor response which was antagonized by phenoxybenzamine. Dose-response studies in dogs provided two nonconvergent dose-response curves, one relating to the pressor effect and the other to the fall in blood pressure. Cardiac output in rabbits and dogs was reduced after ST 155. This reduction in cardiac output may be related to the systemic venodilation caused by ST 155 and hence to a decrease in venous return to the heart. These results are discussed in accordance with the hypothesis that the initial pressor effect of ST 155 results from stimulation of alpha adrenergic receptors and that the hypotensive response involves the central inhibition of an adrenergic mechanism mediating constriction.
Footnotes
- Received July 26, 1967.
- Accepted July 8, 1968.
- © 1968, by The Williams & Wilkins Company
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|