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Pulmonary arterial dysfunction in insulin resistant obese Zucker rats.

Moral-Sanz J, Menendez C, Moreno L, Moreno E, Cogolludo A, Perez-Vizcaino F - Respir. Res. (2011)

Bottom Line: Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases.The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.In 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.

ABSTRACT

Background: Insulin 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.

Methods: Large 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.

Results: Right 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.

Conclusions: In 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.

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Heart wall thickness and BMPR2 expression. (A) Left ventricular (LV), right ventricular (RV) and septal wall thickness from lean (n = 8) and obese (n = 7) Zucker rats. (B) BMPR2 mRNA expression in resistance PA of lean and obese (n = 5) analyzed by RT-PCR and normalized by β-actin expression. (C) BMPR2 precursor (~115 KDa) and mature (~75 KDa) protein expression from obese and lean Zucker lungs (n = 8) analyzed by Western blot and normalized by β-actin expression. Results indicate mean ± s.e.m.
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Figure 1: Heart wall thickness and BMPR2 expression. (A) Left ventricular (LV), right ventricular (RV) and septal wall thickness from lean (n = 8) and obese (n = 7) Zucker rats. (B) BMPR2 mRNA expression in resistance PA of lean and obese (n = 5) analyzed by RT-PCR and normalized by β-actin expression. (C) BMPR2 precursor (~115 KDa) and mature (~75 KDa) protein expression from obese and lean Zucker lungs (n = 8) analyzed by Western blot and normalized by β-actin expression. Results indicate mean ± s.e.m.

Mentions: No significant changes were found in the wall thickness of the right ventricle (RV), the left ventricle (LV) or the septum (S) from obese as compared with lean rats (Figure 1A). The RT-PCR analysis revealed no changes in mRNA transcription levels of BMPR2 gene in resistance PA (Figure 1B) and Western blots showed no significant changes in the whole lung protein expression of BMPR2 or in its heavier precursor (pro-BMPR2) (Figure 1C).


Pulmonary arterial dysfunction in insulin resistant obese Zucker rats.

Moral-Sanz J, Menendez C, Moreno L, Moreno E, Cogolludo A, Perez-Vizcaino F - Respir. Res. (2011)

Heart wall thickness and BMPR2 expression. (A) Left ventricular (LV), right ventricular (RV) and septal wall thickness from lean (n = 8) and obese (n = 7) Zucker rats. (B) BMPR2 mRNA expression in resistance PA of lean and obese (n = 5) analyzed by RT-PCR and normalized by β-actin expression. (C) BMPR2 precursor (~115 KDa) and mature (~75 KDa) protein expression from obese and lean Zucker lungs (n = 8) analyzed by Western blot and normalized by β-actin expression. Results indicate mean ± s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111360&req=5

Figure 1: Heart wall thickness and BMPR2 expression. (A) Left ventricular (LV), right ventricular (RV) and septal wall thickness from lean (n = 8) and obese (n = 7) Zucker rats. (B) BMPR2 mRNA expression in resistance PA of lean and obese (n = 5) analyzed by RT-PCR and normalized by β-actin expression. (C) BMPR2 precursor (~115 KDa) and mature (~75 KDa) protein expression from obese and lean Zucker lungs (n = 8) analyzed by Western blot and normalized by β-actin expression. Results indicate mean ± s.e.m.
Mentions: No significant changes were found in the wall thickness of the right ventricle (RV), the left ventricle (LV) or the septum (S) from obese as compared with lean rats (Figure 1A). The RT-PCR analysis revealed no changes in mRNA transcription levels of BMPR2 gene in resistance PA (Figure 1B) and Western blots showed no significant changes in the whole lung protein expression of BMPR2 or in its heavier precursor (pro-BMPR2) (Figure 1C).

Bottom Line: Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases.The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.In 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.

ABSTRACT

Background: Insulin 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.

Methods: Large 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.

Results: Right 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.

Conclusions: In 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.

Show MeSH
Related in: MedlinePlus