The contractile apparatus in vascular smooth muscle cells of spontaneously hypertensive rats possess increased calcium sensitivity: the possible role of protein kinase C

Soloviev, Anatoly I.; Bershtein, S. A.

doi:10.1097/00004872-199202000-00004

Cited by 32 publications

(25 citation statements)

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“…We have previously investigated the role of PKC in Ca 2+ -sensitization during hypoxic pulmonary hypertension, genetically determined hypertension and hypertension evoked by ionizing irradiation. In all cases, up-regulation of PKCmediated myofilament Ca 2+ -sensitivity was found to play a key role (Soloviev and Bershtein, 1992;Soloviev et al, 1998;.…”

Section: Discussionmentioning

confidence: 94%

“…An increase in ROCK activity, enhanced production of diacylglycerols (DAG) and activation of PKC have all been shown to be associated with various vascular abnormalities, including arterial hypertension in DM (Inoguchi et al, 1992;Soloviev and Bershtein, 1992;Soloviev et al, 1998;Koya and King, 1998;Meier and King, 2000;Idris et al, 2001;Wettschureck and Offermanns, 2002;Curtis et al, 2003;Guo et al, 2003;Seko et al, 2003;Curtis and Scholfield, 2004;Ward et al, 2004;Salamanca and Khalil, 2005;Loirand et al, 2006;Das Evcimen and King, 2007). Taken together, these data suggest that the activation of ROCK and/or PKC may be causally linked to myofilaments Ca 2+ sensitization in the DM-associated hypertensive state.…”

Section: Introductionmentioning

confidence: 89%

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Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats

Kizub

Pavlova

Johnson

et al. 2010

British J Pharmacology

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Background and purpose: Diabetes mellitus (DM) causes multiple dysfunctions including circulatory disorders such as cardiomyopathy, angiopathy, atherosclerosis and arterial hypertension. Rho kinase (ROCK) and protein kinase C (PKC) regulate vascular smooth muscle (VSM) Ca 2+ sensitivity, thus enhancing VSM contraction, and up-regulation of both enzymes in DM is well known. We postulated that in DM, Ca 2+ sensitization occurs in diabetic arteries due to increased ROCK and/or PKC activity. Experimental approach: Rats were rendered hyperglycaemic by i.p. injection of streptozotocin. Age-matched control tissues were used for comparison. Contractile responses to phenylephrine (Phe) and different Ca 2+ concentrations were recorded, respectively, from intact and chemically permeabilized vascular rings from aorta, tail and mesenteric arteries. Key results: Diabetic tail and mesenteric arteries demonstrated markedly enhanced sensitivity to Phe while these changes were not observed in aorta. The ROCK inhibitor HA1077, but not the PKC inhibitor chelerythrine, caused significant reduction in sensitivity to agonist in diabetic vessels. Similar changes were observed for myofilament Ca 2+ sensitivity, which was again enhanced in DM in tail and mesenteric arteries, but not in aorta, and could be reduced by both the ROCK and PKC blockers. Conclusions and implications:We conclude that in DM enhanced myofilament Ca 2+ sensitivity is mainly manifested in muscular-type blood vessels and thus likely to contribute to the development of hypertension. Both PKC and, in particular, ROCK are involved in this phenomenon. This highlights their potential usefulness as drug targets in the pharmacological management of DM-associated vascular dysfunction.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 89%

Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats

Kizub

Pavlova

Johnson

et al. 2010

British J Pharmacology

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“…In contrast, the opposite was seen in the saphenous vein. That aortic and port d vein smooth muscle from spontaneously hypertensive rats possessed greater PKC activity has been reported on the basis of a more pronounced relaxing effect of the PKC inhibitors (Soloviev and Bershtein 1992).…”

Section: Effect ~F Nifedipinementioning

confidence: 98%

Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol esters in pacing-induced heart failure

Förster

1995

Can. J. Physiol. Pharmacol.

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Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13-dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha-phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and without pacing-induced heart failure. The effects of polymyxin B (a relatively selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions developed to PDBu before heart failure, after 1 week of pacing, and at end-stage heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration-dependent increases in contractile force in both the artery and the vein. In the dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced after 1 week of pacing, but returned to control level at end-stage heart failure. In the saphenous vein, the concentration-effect curve to PDBu was displaced to the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x 10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but was less effective with advancing heart failure. In contrast, in the vein, there was a significant increase in inhibitory potential at end-stage heart failure. In all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With the progression of heart failure, the contractions of the saphenous vein, developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin failed to inhibit vascular effects of PDBu. These results are discussed in terms of protein kinase C involvement in vascular contractions and its role in the pathogenesis of heart failure.

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“…It is also recognised that ‘Ca 2+ sensitisation’—the mechanism of vascular contraction that occurs independently of increasing intracellular Ca 2+ levels is another major mechanism that regulates vascular contractility, particularly during hypertension ( Soloviev and Bershtein, 1992 ; Shaw et al ., 1997 ). In particular, the role of rho‐kinase—the predominant mediator of Ca 2+ sensitisation—in the regulation of vascular tone during hypertension has been studied extensively ( Uehata et al ., 1997 ; Chrissobolis and Sobey, 2001 ; Wehrwein et al ., 2004 ; Jin et al ., 2006 ).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the role of rho‐kinase—the predominant mediator of Ca 2+ sensitisation—in the regulation of vascular tone during hypertension has been studied extensively ( Uehata et al ., 1997 ; Chrissobolis and Sobey, 2001 ; Wehrwein et al ., 2004 ; Jin et al ., 2006 ). Furthermore, although early studies suggested that PKC might also contribute to increased vascular contractility during hypertension ( Bruschi et al ., 1988 ; Shibata et al ., 1990 ; Secrest et al ., 1991 ; Soloviev and Bershtein, 1992 ), very few studies have sought to clarify the relative roles of each kinase in hypertension.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of augmented vasoconstriction induced by 5‐hydroxytryptamine in aortic rings from spontaneously hypertensive rats

Budzyn

Ravi

Miller

et al. 2008

British J Pharmacology

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Background and purpose: To test whether development of enhanced vasoconstriction to 5-hydroxytryptamine (5-HT; serotonin) in SHR was temporally related to hypertension, elevated vascular superoxide (O 2 À ) levels, decreased NO bioavailability, or increased contractile effects of cyclooxygenase or rho-kinase and/or PKC. Experimental approach: We examined systolic blood pressure (SBP), vascular O 2 À , and 5-HT-induced contractile responses of aortic segments from 4-and 8-week-old WKY and SHR. Key results: SBP was 35% higher in SHR than WKY at 4 weeks and 60% higher at 8 weeks. Contractile responses to 5-HT were similar in WKY and SHR at 4 weeks, but were markedly augmented in SHR at 8 weeks. The NO synthase inhibitor, L-NAME, enhanced contractile responses to 5-HT markedly in both strains at 4 weeks and in WKY at 8 weeks, but only very modestly in SHR at 8 weeks. These functional differences were associated with higher O 2 À levels in SHR versus WKY at 8 weeks, but not at 4 weeks. The rho-kinase inhibitor, Y-27632, and the PKC inhibitor, Ro 31-8220, each only modestly attenuated contractions in WKY and SHR in each age group, and their effects in each strain were more pronounced at 8 weeks. The cyclooxygenase inhibitor, indomethacin, had no effect on contractile responses. Conclusions and implications: Development of augmented vascular contractile responses to 5-HT in SHR is preceded by hypertension. It is associated with increased vascular O 2 À levels and reduced modulatory effects of NO, and is unlikely to be due to enhanced activity of rho-kinase, PKC or cyclooxygenase.

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The contractile apparatus in vascular smooth muscle cells of spontaneously hypertensive rats possess increased calcium sensitivity: the possible role of protein kinase C

Cited by 32 publications

References 0 publications

Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats

Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats

Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol esters in pacing-induced heart failure

Mechanisms of augmented vasoconstriction induced by 5‐hydroxytryptamine in aortic rings from spontaneously hypertensive rats

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