Nitric oxide‐induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI‐17 and MYPT1

Kitazawa, Takio; Semba, Shingo; Huh, Yang Hoon; Kitazawa, Kazuyo; Eto, Masumi

doi:10.1113/jphysiol.2009.172189

Cited by 45 publications

(77 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the recent work suggests that PKG activates MLCP, thereby inhibiting MLC 20 phosphorylation and contraction [52, [169][170][171] (Fig. 4).…”

Section: Increase Of the Myosin Light-chain Phosphatase (Mlcp) Activitymentioning

confidence: 99%

“…Several recent studies demonstrated that phosphorylation of Ser-695 by PKA/PKG prevents phosphorylation of MYPT-1 at Thr-696 by several kinases and therefore inhibition of MLCP [170,172,173]. Thus, phosphorylation of MYPT-1 by PKA/PKG increases MLCP activity resulting in the decrease in MLC 20 phosphorylation and smooth muscle relaxation [3,[170][171][172]. It is worth mentioning that Nakamura et al reported that Thr-696 phosphorylation decreased by only 50% with 8-Br-cGMP stimulation, whereas the tension of phenylephrine-precontracted arteries and regulatory light-chain phosphorylation fell to baseline, presumably indicating that Ser-695 phosphorylation is not the sole explanation of PKG-induced Ca 2?…”

Section: Increase Of the Myosin Light-chain Phosphatase (Mlcp) Activitymentioning

confidence: 99%

See 1 more Smart Citation

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Morgado

Cairrão

Santos-Silva

et al. 2011

Cell. Mol. Life Sci.

166

131

View full text Add to dashboard Cite

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca(2+) mobilization and Ca(2+) sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca(2+)]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca(2+)]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.

show abstract

“…Most of the recent work suggests that PKG activates MLCP, thereby inhibiting MLC 20 phosphorylation and contraction [52, [169][170][171] (Fig. 4).…”

Section: Increase Of the Myosin Light-chain Phosphatase (Mlcp) Activitymentioning

confidence: 99%

Section: Increase Of the Myosin Light-chain Phosphatase (Mlcp) Activitymentioning

confidence: 99%

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Morgado

Cairrão

Santos-Silva

et al. 2011

Cell. Mol. Life Sci.

166

131

View full text Add to dashboard Cite

show abstract

“…Case-in-point is the work of Mufti et al (39) who showed that ϳ20% of the myogenic response was insensitive to diltiazem, an L-type Ca 2ϩ channel inhibitor. Such observations have fostered the view that there are additional Ca 2ϩ flux pathways that help set cytosolic [Ca 2ϩ ] and thus the level of myogenic tone (10, 25,51). In this context, recent studies have noted that Ca v 3.1 and Ca v 3.2, the ␣ 1 -subunit of T-type Ca 2ϩ channels, are present in resistance arteries (23,41).…”

mentioning

confidence: 99%

Identification of L- and T-type Ca²⁺channels in rat cerebral arteries: role in myogenic tone development

El-Rahman

Harraz

Brett

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

148

View full text Add to dashboard Cite

channel inhibition reduced tone at 20 and 80 mmHg, with the greatest effect at high pressure when the vessel is depolarized. In comparison, the effect of T-type Ca 2ϩ channel blockade on myogenic tone was more limited, with their greatest effect at low pressure where vessels are hyperpolarized. Blood flow modeling revealed that the vasomotor responses induced by T-type Ca 2ϩ blockade could alter arterial flow by ϳ20 -50%. Overall, our findings indicate that L-and T-type Ca 2ϩ channels are expressed in cerebral arterial smooth muscle and can be electrically isolated from one another. Both conductances contribute to myogenic tone, although their overall contribution is unequal. influx from the extracellular space (9). Voltage-gated Ca 2ϩ channels are the principal conductances that regulate extracellular Ca 2ϩ influx. These membrane channels are hetero-oligomeric complexes that comprise a pore-forming ␣ 1 -subunit and accessory proteins that influence gating characteristics and protein trafficking (24). The ␣ 1 -subunit is composed of four domains, each of which contain six transmembrane segments, a S4 voltage sensor, and a P loop that confers ion selectivity (21, 50). Molecular studies have identified three classes of ␣ 1 -subunits (Ca v 1-3), and within each category there are several subtypes. Ca v 1/Ca v 2 subunits display electrical properties characteristic of high voltage-activated Ca 2ϩ channels (i.e., L-, P/Q-, N-, and R types) (5). In contrast, Ca v 3 subunits encode for Ca 2ϩ channels activated by lower voltages (i.e., T type) (20,34 channels was more limited and best observed at lower pressures in hyperpolarized vessels. Although the contribution of the channels to tone development is limited, computational

show abstract

“…For transmission electron microscope (TEM) analysis, mesenteric arterial rings in different organ culture conditions were mounted on the force transducer setup and stretched to adjust the muscle length as described previously (Kitazawa et al 2009). The fresh arterial rings were stretched to 1.2 times their original slack length and the organ-cultured rings were stretched to the same tension level as that of the fresh one.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

2013

Self Cite

View full text Add to dashboard Cite

Background: Chronic treatment with fetal bovine serum (FBS) causes gradual vasoconstriction, vascular wall thickening, and contractility reduction in organ-cultured vascular tissues. We have previously demonstrated that Rho-associated kinase (ROCK) inhibitors prevent the functional alterations of small arteries in response to the FBS treatment. Here, we tested a further hypothesis that the chronic inhibition of ROCK has a protective effect on FBS-induced structural alterations. Methods: To verify the new hypothesis, the rabbit mesenteric arterial rings were cultured in FBS-supplemented culture medium with or without Y-27632, a reversible ROCK inhibitor and then western blot, immunohistochemistry, apoptosis assay, and electron microscopy were performed using organ-cultured arterial rings.

show abstract

Nitric oxide‐induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI‐17 and MYPT1

Cited by 45 publications

References 70 publications

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Identification of L- and T-type Ca²⁺channels in rat cerebral arteries: role in myogenic tone development

ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

Contact Info

Product

Resources

About

Nitric oxide‐induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI‐17 and MYPT1

Cited by 45 publications

References 70 publications

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Identification of L- and T-type Ca2+channels in rat cerebral arteries: role in myogenic tone development

ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

Contact Info

Product

Resources

About

Identification of L- and T-type Ca²⁺channels in rat cerebral arteries: role in myogenic tone development