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.