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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.

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.

Albetol treatment was administered to 31 patients with stable hypertension. The drug produced a drop in the heart rate, cardiac index and a slight decrease of total peripheral resistance, due to albetol simultaneous alpha- and beta-blocking action. There were no marked orthostatic changes. Blood pressure, cardiac index and heart rate values increased to a smaller extent in response to exercise. Experimental studies in the frog atrium showed different effects of Albetol and Propranolol on transmembrane ion currents. Albetol did not affect renal function at rest, nor the pattern of its change under physical stress and in an orthostatic position. It is suggested that albetol alpha-blocking action is predominant in the orthostatic test, while beta-blocking effect prevails during exercise.

The effects of propranolol, oxprenolol, pindolol, labetalol, and atenolol on the isoproterenol-stimulated slow calcium current as well as on spontaneous slow calcium and fast sodium currents were studied in frog trabeculae by the double sucrose bridge technique. Administration of beta-adrenoblockers in low doses (10(-7)-10(-6)M) antagonized the stimulatory effect of isoproterenol on the slow calcium current (pindolol greater than oxprenolol greater than or equal to propranolol = labetalol greater than atenolol). When administered in high doses (2 X 10(-6)-10(-4)M) the beta-adrenoblockers reduced the slow calcium current. Meanwhile, some of them (propranolol, oxprenolol, labetalol) suppressed the fast sodium current.