ABSTRACT
The effect of the new hybrid (beta-, alpha-) adrenoceptor blocking drug proxodolol on cardiac output and its distribution between 16 vascular regions, by using the microsphere method on anesthesized normotensive rats and rats with persistent renovascular hypertension. Proxodolol given in beta-adreno-blocking doses similar to those of labetalol was shown to exert vasodilating effects in normotensive rats. Renal, adrenal, splenic, and skeletal muscle vessels were most sensitive to labetalol, whereas cardiac and pulmonary vessels were responsive to proxodolol. In rats with persistent renovascular hypertension, proxodolol had a vasodilating effect only when it was used in doses inducing alpha-adrenoceptor blockade.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Hemodynamics/drug effects , Oxadiazoles/pharmacology , Vasodilator Agents/pharmacology , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/physiopathology , Labetalol/pharmacology , Labetalol/therapeutic use , Male , Microspheres , Oxadiazoles/therapeutic use , Rats , Vasodilator Agents/therapeutic useABSTRACT
The beta- and alpha-adrenoceptor blocking activity, the specificity of its beta-adrenoceptor blocking action, partial agonistic and membrane-stabilizing properties, as well as antihypertensive, antiarrhythmic, and anti-ischemic effects were studied. Proxodolol was shown to be superior to labetalol in its beta-adrenoceptor blocking action and similar to it in its alpha-adrenoceptor blocking agent. The drug has no a partial agonistic activity and produces a moderate membrane-stabilizing action. Proxodolol proved to be effective in treating experimental hypertension and arrhythmias. It exhibits anti-ischemic activity.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Oxadiazoles/pharmacology , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Animals , Arrhythmias, Cardiac/drug therapy , Cats , Cell Membrane/drug effects , Dogs , Drug Evaluation, Preclinical , Heart/drug effects , Heart Rate/drug effects , Hypertension/drug therapy , In Vitro Techniques , Labetalol/pharmacology , Male , Oxadiazoles/therapeutic use , Oxprenolol/pharmacology , Propranolol/pharmacology , Rabbits , RatsABSTRACT
Wall thickness (w), wall thickness to lumen radius ratio (w/r) and vasomotor reactions produced by electrical stimulation of the sympathetic tract were studied by intravital microscopy of the skeletal muscle (extensor hallucis proprius) and compared in normal Wistar rats (NWR) and spontaneously hypertensive rats (SHR). It was established that w and w/r of arterioles with an equal lumen was greater in SHR than in NWR. Sympathetic stimulation with 6 mA, 3 imp/sec for 10 sec produced an almost 50% reduced arteriolar constriction in SHR, as compared to NWR. Linear positive correlation was shown between w/r and the degree of the lumen narrowing in both groups of animals. A bias for the increase in arteriolar response to neurogenic stimuli was manifested after a drop in blood pressure due to an acute hemorrhage in SHR. It is suggested that high blood pressure in SHR ensures the perfusion of the microcirculatory bed with a constant blood volume and prevents arteriolar constriction.
