Angiotensin II, a unique vasoactive agent dissociates myosin light chain phosphorylation from contraction

Abstract

Angiotensin II (100 nM) induced bi-phasic increases in cytosolic Ca²⁺ level ([Ca²⁺]_i) through the activation of angiotensin Ⅱ type 1 receptor. Pharmacological examinations using 10 μM verapamil, 30 μM La³⁺, and 1 μM thapsigargin indicated that the first phase of the [Ca²⁺]_i-increase was mediated by Ca²⁺ release from sarcoplasmic reticulum (SR) and Ca²⁺ influx independently of voltage dependent Ca²⁺ channel (VDC). In contrast, the second phase of [Ca²⁺]_i-increase was mediated by Ca²⁺ influx through VDC. Although both [Ca²⁺]_i and myosin light chain (MLC)-phosphorylation at the first phase was apparently exceeded the threshold for contraction as estimated by high K⁺-induced responses, there was no appreciable contraction, indicating the dissociation between MLC phosphorylation and force during this phase. In contrast, the second phase of [Ca²⁺]_i was associated with the increases in both MLC phosphorylation and force. These results suggest that angiotensin II is a unique agonist which dissociates MLC-phosphorylation from muscle force during the Ca²⁺ releases from SR.