Limits...
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.

Show MeSH

Related in: MedlinePlus

Vasoconstrictor responses in resistance PA. (A) Contractile responses of resistance PA induced by KCl (80 mM, n = 8, left), hypoxia (n = 3, middle) and phenyleprine (10-7 M, n = 3-4, right) in resistance PA from lean and obese Zucker rats. (B) Concentration-response curve to 5-HT (n = 6). (C) Whole lung protein expression of 5-HT2A receptor (n = 8). Results indicate mean ± s.e.m. *, ** denote P < 0.05 and P < 0.01 respectively, obese vs lean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3111360&req=5

Figure 5: Vasoconstrictor responses in resistance PA. (A) Contractile responses of resistance PA induced by KCl (80 mM, n = 8, left), hypoxia (n = 3, middle) and phenyleprine (10-7 M, n = 3-4, right) in resistance PA from lean and obese Zucker rats. (B) Concentration-response curve to 5-HT (n = 6). (C) Whole lung protein expression of 5-HT2A receptor (n = 8). Results indicate mean ± s.e.m. *, ** denote P < 0.05 and P < 0.01 respectively, obese vs lean.

Mentions: The contractile response to 80 mM KCl in resistance PA showed a significant reduction in obese compared to lean rats. Obese rats also evidenced a significant hyporesponsiveness to hypoxia, phenylephrine and 5-HT (Figure 5 and Table 1). We further investigated the response to the 5-HT2 agonist α-methyl-5-HT. This agonist also showed reduced vasoconstriction responses in PA rings from obese rats (Table 1). Western blot analysis of whole lung homogenates revealed no changes in the expression of 5-HT2A receptors.


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)

Vasoconstrictor responses in resistance PA. (A) Contractile responses of resistance PA induced by KCl (80 mM, n = 8, left), hypoxia (n = 3, middle) and phenyleprine (10-7 M, n = 3-4, right) in resistance PA from lean and obese Zucker rats. (B) Concentration-response curve to 5-HT (n = 6). (C) Whole lung protein expression of 5-HT2A receptor (n = 8). Results indicate mean ± s.e.m. *, ** denote P < 0.05 and P < 0.01 respectively, obese vs lean.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Vasoconstrictor responses in resistance PA. (A) Contractile responses of resistance PA induced by KCl (80 mM, n = 8, left), hypoxia (n = 3, middle) and phenyleprine (10-7 M, n = 3-4, right) in resistance PA from lean and obese Zucker rats. (B) Concentration-response curve to 5-HT (n = 6). (C) Whole lung protein expression of 5-HT2A receptor (n = 8). Results indicate mean ± s.e.m. *, ** denote P < 0.05 and P < 0.01 respectively, obese vs lean.
Mentions: The contractile response to 80 mM KCl in resistance PA showed a significant reduction in obese compared to lean rats. Obese rats also evidenced a significant hyporesponsiveness to hypoxia, phenylephrine and 5-HT (Figure 5 and Table 1). We further investigated the response to the 5-HT2 agonist α-methyl-5-HT. This agonist also showed reduced vasoconstriction responses in PA rings from obese rats (Table 1). Western blot analysis of whole lung homogenates revealed no changes in the expression of 5-HT2A receptors.

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