Differential expression of the enzymes regulating myosin light chain phosphorylation are responsible for the slower relaxation of pulmonary artery than mesenteric artery in rats.

While arterial tone is generally determined by the phosphorylation of Ser in myosin light chain (p-MLC2), Thr/Ser diphosphorylation of MLC2 (pp-MLC2) has been suggested to hinder the relaxation of smooth muscle. In a dual-wire myography of rodent pulmonary artery (PA) and mesenteric artery (MA), we noticed significantly slower relaxation in PA than in MA after 80 mM KCl-induced condition (80K-contraction). Thus, we investigated the MLC2 phosphorylation and the expression levels of its regulatory enzymes; soluble guanylate cyclase (sGC), Rho-A dependent kinase (ROCK) and myosin light chain phosphatase target regulatory subunit (MYPT1).

Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.

Obscurins are giant cytoskeletal proteins with structural and regulatory roles. Obscurin-B (~870 kDa), the largest known isoform, contains 2 enzymatically active Ser/Thr kinase (kin) domains, kin1 and kin2, which belong to the myosin light chain kinase family. Kin1 binds to and phosphorylates N-cadherin, a major component of the intercalated disc, the unique sarcolemmal microdomain that mediates the mechanochemical coupling of adjacent cardiomyocytes.

T18/S19 diphosphorylation of myosin regulatory light chain impairs pulmonary artery relaxation in monocrotaline-induced pulmonary hypertensive rats.

Phosphorylation of Ser19 (S19-p) on the myosin regulatory light chain (MLC2) is critical for arterial contraction. It has been shown that elevated RhoA-dependent kinase (ROCK) activity or decreased MLC phosphatase (MLCP) activity leads to further phosphorylation of Thr18 (T18/S19-pp), which has been linked to vasospastic diseases. However, this phenomenon has not yet been studied in the context of pulmonary arterial hypertension (PAH).

The novel K7 channel activator URO-K10 exerts enhanced pulmonary vascular effects independent of the KCNE4 regulatory subunit.

K7 channels exert a pivotal role regulating vascular tone in several vascular beds. In this context, K7 channel agonists represent an attractive strategy for the treatment of pulmonary arterial hypertension (PAH). Therefore, in this study, we have explored the pulmonary vascular effects of the novel K7 channel agonist URO-K10.

Discovery and characterization of a potent activator of the BK channel that relives overactive bladder syndrome in rats.

The large-conductance Ca-activated K channel (BK channel) is involved in repolarizing the membrane potential and has a variety of cellular functions. The BK channel is highly expressed in bladder smooth muscle and mediates muscle relaxation. Compounds that activate the BK channel have therapeutic potential against pathological symptoms associated with the overactivity of bladder smooth muscle.

The effect of fibroblast growth factor receptor inhibition on resistance exercise training-induced adaptation of bone and muscle quality in mice.

Aging in mammals, including humans, is accompanied by loss of bone and muscular function and mass, characterized by osteoporosis and sarcopenia. Although resistance exercise training (RET) is considered an effective intervention, its effect is blunted in some elderly individuals. Fibroblast growth factor (FGF) and its receptor, FGFR, can modulate bone and muscle quality during aging and physical performance.

Downregulation of Soluble Guanylate Cyclase and Protein Kinase G With Upregulated ROCK2 in the Pulmonary Artery Leads to Thromboxane A2 Sensitization in Monocrotaline-Induced Pulmonary Hypertensive Rats.

Thromboxane A2 (TXA) promotes various physiological responses including pulmonary artery (PA) contraction, and pathophysiological implications have been suggested in cardiovascular diseases including pulmonary hypertension. Here, we investigated the role of TXA receptor (TP)-mediated signaling in the pathophysiology of pulmonary arterial hypertension (PAH). The sensitivity of PA to the contractile agonist could be set by relaxing signals such as the nitric oxide (NO), soluble guanylate cyclase (sGC), and cGMP-dependent kinase (PKG) pathways.

Increased inward rectifier K current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium-dependent relaxation via Ca -activated K channels.

Endothelium-dependent vasorelaxation is partly mediated by small-conductance (SK3) and intermediate-conductance Ca -activated K channels (SK4) in the endothelium that results in endothelium-dependent hyperpolarization (EDH). Apart from the electrical propagation through myoendothelial gap junctions, the K released from the endothelium facilitates EDH by increasing inward rectifier K channel (Kir) conductance in smooth muscle cells. The EDH-dependent relaxation of coronary artery (CA) and Kir current in smooth muscle cells (CASMCs) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart.

The Effects of Progressive Resistance Exercise on Recovery Rate of Bone and Muscle in a Rodent Model of Hindlimb Suspension.

This study aimed to examine the exercise-mediated musculoskeletal recovery following hindlimb suspension (HS) in order to identify whether bone modeling and muscle hypertrophy would eventuate in a synchronized manner during recovery stage. To identify whether 2-week HS would be sufficient to induce a significant reduction of physiological indices in both tibia and adjacent hindlimb muscles, a total of 20 rats was randomized into 2-week HS ( = 10) and age-matched control group ( = 10, CON). Another batch of rats were randomly assigned to three different groups to identify recovery intervention effects following suspension: (1) 2-week HS followed by 4-week spontaneous reloading recovery (HRE, = 7).