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Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.

Gálvez-Prieto B, Somoza B, Gil-Ortega M, García-Prieto CF, de Las Heras AI, González MC, Arribas S, Aranguez I, Bolbrinker J, Kreutz R, Ruiz-Gayo M, Fernández-Alfonso MS - Front Pharmacol (2012)

Bottom Line: This anticontractile effect was endothelium-dependent.Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium.In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

View Article: PubMed Central - PubMed

Affiliation: Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid Madrid, Spain.

ABSTRACT
Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10(-9) M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

No MeSH data available.


Related in: MedlinePlus

Concentration-response curve to leptin (10−10 to 10−8 M) (A) and acetylcholine (10−9 to 10−4 M) (B) in aortic rings from WKY and SHR. Concentration-response curve to Ach in aortic rings from WKY (C) and SHR (D) in presence and absence of PVAT. Relaxation is expressed as percentage of a previous contraction to U46619 (10−7 M). Data are shown as mean ± SEM of 10 animals per strain.
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Figure 4: Concentration-response curve to leptin (10−10 to 10−8 M) (A) and acetylcholine (10−9 to 10−4 M) (B) in aortic rings from WKY and SHR. Concentration-response curve to Ach in aortic rings from WKY (C) and SHR (D) in presence and absence of PVAT. Relaxation is expressed as percentage of a previous contraction to U46619 (10−7 M). Data are shown as mean ± SEM of 10 animals per strain.

Mentions: Leptin (10−10 to 10−8 M) induced a concentration-dependent vasodilation in aortic rings from WKY, which was almost abolished in arteries from SHR (Figure 4A). Vasodilatory effect of leptin was weak reaching a maximal response of 30 and of 5% of previous contraction in WKY and SHR, respectively. Endothelium removal and incubation with 0.1 mM L-NAME completely abolished relaxation to leptin (results nor shown), suggesting the involvement of NO in this response, as previously observed in rat aorta (Kimura et al., 2000; Lembo et al., 2000).


Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.

Gálvez-Prieto B, Somoza B, Gil-Ortega M, García-Prieto CF, de Las Heras AI, González MC, Arribas S, Aranguez I, Bolbrinker J, Kreutz R, Ruiz-Gayo M, Fernández-Alfonso MS - Front Pharmacol (2012)

Concentration-response curve to leptin (10−10 to 10−8 M) (A) and acetylcholine (10−9 to 10−4 M) (B) in aortic rings from WKY and SHR. Concentration-response curve to Ach in aortic rings from WKY (C) and SHR (D) in presence and absence of PVAT. Relaxation is expressed as percentage of a previous contraction to U46619 (10−7 M). Data are shown as mean ± SEM of 10 animals per strain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367267&req=5

Figure 4: Concentration-response curve to leptin (10−10 to 10−8 M) (A) and acetylcholine (10−9 to 10−4 M) (B) in aortic rings from WKY and SHR. Concentration-response curve to Ach in aortic rings from WKY (C) and SHR (D) in presence and absence of PVAT. Relaxation is expressed as percentage of a previous contraction to U46619 (10−7 M). Data are shown as mean ± SEM of 10 animals per strain.
Mentions: Leptin (10−10 to 10−8 M) induced a concentration-dependent vasodilation in aortic rings from WKY, which was almost abolished in arteries from SHR (Figure 4A). Vasodilatory effect of leptin was weak reaching a maximal response of 30 and of 5% of previous contraction in WKY and SHR, respectively. Endothelium removal and incubation with 0.1 mM L-NAME completely abolished relaxation to leptin (results nor shown), suggesting the involvement of NO in this response, as previously observed in rat aorta (Kimura et al., 2000; Lembo et al., 2000).

Bottom Line: This anticontractile effect was endothelium-dependent.Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium.In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

View Article: PubMed Central - PubMed

Affiliation: Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid Madrid, Spain.

ABSTRACT
Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10(-9) M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

No MeSH data available.


Related in: MedlinePlus