Pulmonary arterial dysfunction in insulin resistant obese Zucker ratsReport as inadecuate

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Respiratory Research

, 12:51

First Online: 01 December 2011Received: 02 November 2010Accepted: 22 April 2011


BackgroundInsulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.

MethodsLarge and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.

ResultsRight ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance but not in conductance pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents hypoxia, phenylephrine and 5-HT was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.

ConclusionsIn contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.

List of abbreviationsAChacetylcholine

BMPR2bone morphogenetic protein receptor 2

Emaxmaximum response

LVleft ventricle

PApulmonary arteries

PAHpulmonary arterial hypertension

PASMCpulmonary artery smooth muscle cells

pD2negative logarithm of the molar concentration that causes 50% of the maximum response

RVright ventricle


Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-51 contains supplementary material, which is available to authorized users.

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Author: Javier Moral-Sanz - Carmen Menendez - Laura Moreno - Enrique Moreno - Angel Cogolludo - Francisco Perez-Vizcaino

Source: https://link.springer.com/

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