Tetramethylpyrazine Suppresses the Enhanced Ca2+ Sensitivity through Inhibiting the Expression of RhoA-ROCK in Artery of Simulated Weightlessness Rats

Abstract Under weightlessness condition, the vasoconstriction will present the regional specific change. This study is to explore the role of myofilament Ca2+ sensitivity and its regulator RhoA-ROCK in these alterations, and the effect of tetramethylpyrazine on it. Female SD Rats tail suspending was used to simulate weightlessness. This study found that in weightless carotid artery, the vasoconstriction induced by PHE and KCl enhanced. The Ca2+ sensitivity, the protein expression of RhoA and ROCK II, and the phosphorylation level of MYPT1 and MLC increased. Tetramethylpyrazine administration for weightless rats could weaken the vasoconstriction, decrease the Ca2+ sensitivity, and reduce the above protein expressions and phosphorylation levels. Pretreatment with Y-27632 to inhibit the ROCK activity could decrease the vasoconstriction and the Ca2+ sensitivity in weightless rats, but have no effect in weightlessness plus tetramethylpyrazine administration rats. In weightless mesenteric artery, the vasoconstriction weakened. The Ca2+ sensitivity, the above protein expressions and phosphorylation levels decreased. Both tetramethylpyrazine administration and pretreatment with Y-27632 had no effects in weightlessness rats. These results suggest that the distinct alteration of myofilament Ca2+ sensitivity regulated by RhoA-ROCK possibly is the key factor resulting in the weightless vasoconstriction presenting different changes. Tetramethylpyrazine can inhibit the RhoA-ROCK protein expression to depress the enhanced weightless vasoconstriction in anterior part of body, but has no influence on the weakened vasoconstriction in posterior part of body. The present study clarifies the change of Ca2+ sensitivity and its mechanism in weightless artery, and broadens the application of tetramethylpyrazine in the treatment of vascular weightless dysfunction.