Frequency selective compounds and inhibition of cardiovascular reflexes

Abstract

In anesthetized normotensive rats, several classes of antihypertensive agents (i.v. injection) were compared for their effects on mean arterial pressure (MAP) and reflex-induced changes in MAP produced by 45 degrees head-up tilt, bilateral carotid occlusion (BCO) and stimulation of the central end of sciatic nerves (SNS). Two doses which produced average MAP fall of 32 to 47 mm Hg were used for comparison. Guanethidine (1 and 3 mg/kg) depressed markedly not only the tilt responses but also responses to BCO and SNS. In contrast, clonidine (2 and 6 micrograms/kg) or dopamine2 receptor agonists, apomorphine (100 and 300 micrograms/kg) and VICO-81 (trans-6,9-dimethoxy-1-n-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g] quinoline, 60 and 200 micrograms/kg), only prolonged the time required for compensation. Apomorphine inhibited BCO reflexes slightly, not affecting SNS-induced responses. However, neither the BCO nor the SNS responses were influenced by VICO-81. On the other hand, serotonin1A receptor agonists, (8-hydroxy-2-di-n-propylaminotetralin, 100 and 300 micrograms/kg) and PM-1000 (10-methyl-11-hydroxyaporphine, 1 and 3 mg/kg), did not inhibit responses to tilt. MAP during tilt was somewhat higher than controls after the two serotonin1A receptor agonists. Although BCO or SNS was not influenced by 8-hydroxy-2-di-n-propylaminotetralin, both responses were depressed slightly by higher doses of PM-1000 (3 mg/kg). To correlate the degree of inhibition on tilt reflex with that on sympathetic neurotransmission after these hypotensive agents, plasma catecholamines, norepinephrine, epinephrine and dopamine, were measured.(ABSTRACT TRUNCATED AT 250 WORDS)