Disordered calcium homeostasis can lead to endoplasmic reticulum (ER) stress. Our previous data showed that time course activation of ER stress contributes to time-related increase in ischemia-reperfusion (I/R) injury. However, it has not been tested whether PI3K/Akt and JAK2/STAT3 pathways play differential roles in reducing ER stress to protect the heart. In the present study, using fasudil w...

OBJECTIVE: Leukocyte adhesion in retinal microvasuculature substantially contributes to diabetic retinopathy (DR). Involvement of the Rho/ROCK pathway in diabetic microvasculopathy and therapeutic potential of fasudil, a selective ROCK inhibitor, are investigated. RESEARCH DESIGN AND METHODS: Localization of RhoA/ROCK and Rho activity were examined in rats’ retinal tissues. Impact of intravitre...

A decrease in environmental temperature can directly affect the contractility of cutaneous vasculature, mediated in part by alpha(2)-adrenoceptors. Most of the cellular mechanisms underlying the cooling-enhanced contractility to alpha(2)-adrenoceptor agonists have been reported in cutaneous arteries but little information is available on cutaneous veins. To investigate the cellular mechanisms a...

Primary human aging may be associated with augmented Rho kinase (ROCK)-mediated contraction of vascular smooth muscle and ROCK-mediated inhibition of nitric oxide synthase (NOS). We hypothesized that the contribution of ROCK to reflex vasoconstriction (VC) is greater in aged skin. Cutaneous VC was elicited by 1) whole body cooling [mean skin temperature (T(sk)) = 30.5 degrees C] and 2) local no...

BACKGROUND In recent years, the alleviation of acute myocardial ischemia and reperfusion injury (MI/RI) during myocardial reperfusion has presented a significant clinical challenge. This study was performed to investigate the effects of fasudil hydrochloride (FH) postconditioning on MI/RI and the underlying mechanism. METHODS Seventy-two rats were randomly divided into four groups: a Sham gro...

This study was performed to determine the effectiveness of the Rho kinase inhibitor and NF-kappaB inhibitor in renal injury of ANG II-infused hypertensive rats. Male Sprague-Dawley rats, maintained on a normal diet, received either a sham operation (n = 7) or continuous ANG II infusion (120 ng/min) subcutaneously via minipumps. The ANG II-infused rats were further subdivided into three subgroup...

This study investigated the effect of the Rho kinase inhibitor Y-27632 and fasudil on the development of human mesangial cell (HMC) inflammation and fibrosis induced by high glucose and to clarify the contribution of the Rho/ROCK signaling pathway in the pathogenesis of diabetic kidney disease (DKD). High glucose (30 mmol/l) induced the Rho/ROCK signaling pathway. Western blotting was used to d...

Cold-induced vasoconstriction in cutaneous blood vessels is mediated in part by increased activity of vascular smooth muscle alpha2-adrenoceptors (VSM alpha2-ARs). In mouse cutaneous arteries, alpha2C-ARs are normally silent at 37 degrees C but mediate cold-induced augmentation of alpha2-AR responsiveness. In transfected HEK293 cells, this functional rescue is mediated by cold-induced transloca...