Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive ratsReport as inadecuate




Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 10:48

First Online: 02 June 2011Received: 14 March 2011Accepted: 02 June 2011

Abstract

ObjectiveInsulin resistance, diabetes, and hypertension are considered elements of metabolic syndrome which is associated with vascular dysfunction. We investigated whether inhibition of protein kinase C PKC would affect vascular function in diabetic hypertensive DH rats.

MethodsA combination of type 2 diabetes and arterial hypertension was produced in male Sprague Dawley rats by intrauterine protein deprivation IUPD followed by high salt diet. At the age of 32 weeks, DH rats were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril Capto, 30 mg-kg, PKC inhibitor ruboxistaurin RBX, 50 mg-kg or vehicle n = 8 per group and blood pressure was monitored using telemetry. At the end of experiments, femoral arteries were dissected, and vascular reactivity was evaluated with isovolumic myography.

ResultsThe IUPD followed by high salt diet resulted in significant elevation of plasma glucose, plasma insulin, and blood pressure. Endothelium-dependent vascular relaxation in response to acetylcholine was blunted while vascular contraction in response to phenylephrine was enhanced in the DH rats. Neither Capto nor RBX restored endothelium-dependent vascular relaxation while both suppressed vascular contraction. Ex-vivo incubation of femoral arteries from control rats with insulin induced dose-response vasorelaxation while insulin failed to induce vasorelaxation in the DH rat arteries. In the control arteries treated with endothelial nitric oxide synthase inhibitor L-NAME, insulin induced vasoconstriction that was exacerbated in DH rats. Capto and RBX partially inhibited insulin-stimulated vascular contraction.

ConclusionThese findings suggest that PKC inhibition ameliorates functional endothelial insulin resistance and smooth muscle cell hypersensitivity to insulin, but does not restore acetylcholine-activated endothelium-dependent vasodilation in DH rats.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-10-48 contains supplementary material, which is available to authorized users.

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Author: Xiao Lu - James S Bean - Ghassan S Kassab - Mark D Rekhter

Source: https://link.springer.com/article/10.1186/1475-2840-10-48







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