Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed

Büyükafşar, Kansu; Arıkan, Onur; Ark, Mustafa; Secilmis, Ata; Ün, İsmail; Şingirik, Ergin

doi:10.1016/j.ejphar.2003.11.076

Cited by 21 publications

(13 citation statements)

References 36 publications

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“…Contrasting results have also been reported in studies of vascular reactivity. Although several studies suggest that NO-induced relaxation is, in part, attenuated by a rho kinase-mediated mechanism (2, 6), rho kinase-mediated contractions to phenylephrine were not affected by removal of endothelium, deficiency of eNOS, or inhibition of NOS and guanylyl cyclase (4,29). It is unlikely that the acute administration of a rho kinase inhibitor as in the present study affected eNOS expression or the levels of Larginine but rather activation of eNOS.…”

Section: Discussioncontrasting

confidence: 53%

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Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Nuno

Harrod

Lamping

2009

American Journal of Physiology-Heart and Circulatory Physiology

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The objective of this study was to determine if mechanisms involved in vascular dysfunction in type 2 diabetes differ with sex. Vascular reactivity, expression, and activation of rhoA and rho kinase were measured in aorta from male and female nondiabetic C57BLKS/J and diabetic BKS.Cg-m(+/+) Lepr(db)/J (db/db) mice, a model of type 2 diabetes. Relaxation to acetylcholine and nitroprusside was similar in aorta from nondiabetic male and female mice. Relaxation to acetylcholine was reduced approximately 50% in both male and female diabetic mice. Although inhibition of rho kinase with H-1152 increased relaxation to acetylcholine and nitroprusside in nondiabetic males, it had no effect on the response in either nondiabetic or diabetic females or diabetic males. Contraction to serotonin was increased similarly in male and female diabetic mice compared with nondiabetic mice and was reduced following inhibition of rho kinase with either fasudil or H-1152. Activation of rhoA and its downstream effector, rho kinase, was greater in aorta from diabetic males compared with nondiabetic males. In contrast, there were no differences in vascular activation of rhoA or rho kinase in diabetic females. The increased activity of rhoA and rho kinase in diabetic mice was not due to a change in protein expression of rhoA or rho kinase (ROCK1 and ROCK2) in vessels from either males or females. Although contractile dysfunction in vessels occurs in both male and female diabetic mice, the dysfunction in diabetic males is dependent upon activation of rhoA and rho kinase. Alternative mechanisms affecting rho kinase activation may be involved in females.

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Section: Discussioncontrasting

confidence: 53%

“…RhoA and NO inversely affect the expression and activation of the opposing signaling pathways in some (6,26,(41)(42)(43)(44)47) but not all studies (4,29,48). The magnitude and impact of this interaction may depend on cell type, tissue, animal, or disease state.…”

mentioning

confidence: 92%

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Nuno

Harrod

Lamping

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…ROK inhibition with Y-27632 significantly reduced PE-induced constriction in small femoral arteries (ϳ130 m) (22) and effectively reversed PE-mediated constriction but not ET-1-mediated constriction in a perfused mesenteric bed (6). Similarly, myogenic tone is ROK mediated in small cerebral arteries (17).…”

Section: Discussionmentioning

confidence: 97%

ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats

Allahdadi¹,

Walker²,

Kanagy³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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We reported previously that intermittent hypoxia with CO(2) to maintain eucapnia (IH-C) elevates plasma endothelin-1 (ET-1) and arterial pressure. In small mesenteric arteries (sMA; inner diameter = 150 microm), IH-C augments ET-1 constrictor sensitivity but diminishes ET-1-induced increases in intracellular Ca(2+) concentration, suggesting IH-C exposure increases both ET-1 levels and ET-1-stimulated Ca(2+) sensitization. Because Rho-associated kinase (ROK) can mediate Ca(2+) sensitization, we hypothesized that augmented vasoconstrictor sensitivity to ET-1 in arteries from IH-C-exposed rats is dependent on ROK activation. In thoracic aortic rings, ET-1 contraction was not different between groups, but ROK inhibition (Y-27632, 3 and 10 microM) attenuated ET-1 contraction more in IH-C than in sham arteries (50 +/- 11 and 78 +/- 7% vs. 41 +/- 12 and 48 +/- 9% inhibition, respectively). Therefore, ROK appears to contribute more to ET-1 contraction in IH-C than in sham aorta. In sMA, ROK inhibitors did not affect ET-1-mediated constriction in sham arteries and only modestly inhibited it in IH-C arteries. In ionomycin-permeabilized sMA with intracellular Ca(2+) concentration held at basal levels, Y-27632 did not affect ET-1-mediated constriction in either IH-C or sham sMA and ET-1 did not stimulate ROK translocation. In contrast, inhibition of myosin light-chain kinase (ML-9, 100 microM) prevented ET-1-mediated constriction in sMA from both groups. Therefore, IH-C exposure increases ET-1 vasoconstrictor sensitivity in sMA but not in aorta. Furthermore, ET-1 constriction is myosin light-chain kinase dependent and mediated by Ca(2+) sensitization that is independent of ROK activation in sMA but not aorta. Thus ET-1-mediated signaling in aorta and sMA is altered by IH-C but is dependent on different second messenger systems in small vs. large arteries.

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“…Because the importance of activation of Rho-associated kinases in mediating constriction in the vasculature has been shown to be variable depending on the agonist [50], it is important to examine specifically the magnitude of involvement in S1P-mediated vasoconstriction. The significant presence of message for S1P-specific receptors known to signal through Rho-associated kinases (S1P 2 /EDG5 and S1P 3 /EDG3), the dose-dependent relaxation to Y27632 (an effective inhibitor of both ROCK1 and ROCK2), and the considerable involvement of Ca 2þ -sensitization in the response to S1P demonstrate the importance of this signaling pathway for tone development in human placental arteries.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-Phosphate Acts via Rho-Associated Kinase and Nitric Oxide to Regulate Human Placental Vascular Tone1

Hemmings

Hudson

Halliday

et al. 2006

Biology of Reproduction

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Sphingosine-1-phosphate (S1P), a bioactive lipid released from activated platelets, has been demonstrated in animal models to regulate vascular tone through receptor-mediated activation of Rho-associated kinase 1 and nitric oxide synthase 3. The role of S1P in regulation of human vascular tone (particularly during pregnancy, with its unique vascular adaptations and localized platelet activation) is unknown. We hypothesized that S1P would constrict small placental arteries through activation of Rho-associated kinases with modulation by nitric oxide. Reverse transcription-polymerase chain reaction of chorionic plate artery preparations detected mRNAs encoding all five receptors for S1P, and S1P induced dose-dependent vasoconstriction of both chorionic plate and stem villous isobarically mounted arteries, which at 10 micromol/L was 32.9% +/- 3.86% (mean +/- SEM) and 34.6% +/- 7.01%, respectively. In stem villous arteries, S1P-induced vasoconstriction was enhanced significantly following inhibition of nitric oxide synthases with N(G)-nitro-L-arginine methyl ester (100 micromol/L, 52.6% +/- 6.28%, P < 0.05). The S1P-induced vasoconstriction was reversed by Y27632, an inhibitor of Rho-associated kinases (10 micromol/L) in both chorionic plate (to 14.9% +/- 4.95%) and stem villous arteries (to 2.71% +/- 6.13%). The S1P added to alpha-toxin-permeabilized, isometrically mounted chorionic plate arteries bathed in submaximal Ca(2+)-activating solution induced Ca(2+)-sensitization of constriction, which was 47.7% +/- 10.0% of that occurring to maximal Ca(2+)-activating solution. This was reduced by Y27632 to 18.4% +/- 18.4%. Interestingly, S1P-induced vasoconstriction occurred in all isobarically mounted arteries but was inconsistent in isometrically mounted chorionic plate arteries. In summary, S1P-induced vasoconstriction in human placental arteries is mediated by increased Ca(2+)-sensitization through activation of Rho-associated kinases, and this vasoconstriction also is modulated by nitric oxide. Identification of these actions of S1P in the placental vasculature is important for understanding both normal and potentially abnormal vascular adaptations with pregnancy.

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Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed

Cited by 21 publications

References 36 publications

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice

ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats

Sphingosine-1-Phosphate Acts via Rho-Associated Kinase and Nitric Oxide to Regulate Human Placental Vascular Tone1

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