Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride.
Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a "Ca-antagonist" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed.
Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride. Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a "Ca-antagonist" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed.