28-Day hindlimb unweighting reduces expression of Rho kinase and inhibits its effects in femoral artery of rat

Abstract

Previous studies have demonstrated inconsistent roles of Rho kinase (ROCK) in the decreased vasoconstriction of rat hindquarter vessels induced by hindlimb unweighting (HU). The present study was designed to determine the unclear role of ROCK in the mediation of HU-induced decreased femoral arterial vasoconstriction. 28-day HU rat was adopted as the animal model. With or without Y-27632, a ROCK inhibitor, isometric force of femoral artery was measured. The expression of ROCK and its effects on downstream targets were also examined. Results showed that (1) HU caused a significant decrease of the phenylephrine (PE)-evoked and potassium chloride (KCl)-evoked femoral arterial vasoconstriction (P < 0.05), confirming the functional findings by previous studies. (2) Inhibition of ROCK with Y-27632 produced an equal reduction of the vasoconstriction in CON and HU. (3) HU significantly decreased ROCK II expression and the effects of ROCK on myosin light-chain phosphatase (MLCP) and MLC (P < 0.05), but increased p65 nuclear translocation (P < 0.05) and inducible nitric oxide synthase (iNOS) expression (P < 0.05). (4) HU significantly (P < 0.05) increased NO production in femoral arteries, with Y-27632 significantly (P < 0.01) amplifying this effect. These findings have revealed that 28-day HU reduced the expression and effects of ROCK on downstream targets both directly (MLCP and MLC) and possibly indirectly (NF-κB/iNOS/NO pathway) related to vasoconstriction in femoral arteries.

The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway

“…Data from our previous studies demonstrated that simulated microgravity promotes monocyte adhesion to the rat aortic endothelium, which is modulated by NF-κB activation (Liu et al 2015). Moreover, Wang et al reported that simulated microgravity might reduce the effects of ROCK on vasoconstriction in the femoral artery by activating the NF-κB pathway (Wang et al 2015). The present study demonstrated that simulated microgravity promoted IκBα degradation and NF-κB activation in rat common carotid artery.…”

BKCa compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind‐limb unweighted rats

“…Rodents experiencing real spaceflight exhibited increased vasoconstriction of the cerebral artery but decreased vasoconstriction of the mesenteric and skeletal muscle resistance arteries (26,27). Numerous ground-based simulated microgravity studies by HU rats and bed-resting humans have also shown hypertrophy and increased vasoconstriction of the cerebral and carotid arteries but atrophy and decreased vasoconstriction of abdominal, mesenteric, and femoral arteries (4,5,(10)(11)(12)(13)(14)28). However, as one of the most significant members of the artery system owning vital importance for the replenishment of the heart, coronary vasoactive adaptations induced by real and simulated microgravity has not yet been reported.…”

“…1 and 6-8, both cardiac mass and left-ventricular diastolic volume were found to be decreased by real and simulated microgravity, indicating compromised cardiac function. Our previous studies have demonstrated regional specific remodeling of the vasculature in the hind-limb unweighted (HU) rat, an animal model simulating deconditioning effects of microgravity on the cardiovascular system (9), which exhibited as hypertrophy and hyperreactivity of the forebody arteries including cerebral and carotid arteries as well as atrophy and hyporeactivity of the hind-body arteries, such as mesenteric and femoral arteries (4,(10)(11)(12)(13)(14). However, as one of the most important members of the artery system circulating the heart, the coronary artery has not yet been fully studied about its ABBREVIATIONS: AUC, area under the curve; BK Ca , large-conductance Ca 2+activated potassium channel; BSA, bovine serum albumin; C3, clostridium botulitum C3 exoenzyme; Con, control; CRC, concentration-response curve; Emax, maximal constriction; HU, hind-limb unweighted; IBTX, iberiotoxin; MLC, myosin light chain; MYPT-1, myosin light chain phosphatase target-1; phospho, phosphorylated; PSS, physiologic salt solution; RCA, right coronary artery; RhoA, Ras homolog family member A; ROCK, Rho kinase; TBS-T, Tris-buffered saline containing 0.1% Tween 20; VSMC, vascular smooth muscle cell adaptations under microgravity conditions.…”

“…1 and 6-8, both cardiac mass and left-ventricular diastolic volume were found to be decreased by real and simulated microgravity, indicating compromised cardiac function. Our previous studies have demonstrated regional specific remodeling of the vasculature in the hind-limb unweighted (HU) rat, an animal model simulating deconditioning effects of microgravity on the cardiovascular system (9), which exhibited as hypertrophy and hyperreactivity of the forebody arteries including cerebral and carotid arteries as well as atrophy and hyporeactivity of the hind-body arteries, such as mesenteric and femoral arteries (4,(10)(11)(12)(13)(14). However, as one of the most important members of the artery system circulating the heart, the coronary artery has not yet been fully studied about its adaptations under microgravity conditions.…”

Intermittent short‐duration reoxygenation protects against simulated high altitude‐induced pulmonary hypertension in rats

“…The arteries were carefully dissected under a microscope and cut into 3-mm lengths. Isometric force measurement was performed according to the methods described by Wang et al 13 In brief, pulmonary artery rings were mounted onto two gracile steel hooks and suspended in a four-chamber organ bath system (Radnoti, Covina, CA, USA), with one hook attached to the holder in the chamber and the other to the transducer connected to PowerLab (AD Instruments, Bella Vista NSW, Australia) for vasoreactivity recording. The chambers were filled with Krebs solution, kept at 37°C, and continuously bubbled with 95% O 2 and 5% CO 2 .…”