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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

Effect of leptin on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (A) and SHR (B). Effect of endothelial denudation on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (C) and SHR (D) in absence and presence of leptin. Data are shown in milligram as mean ± SEM of 10 animals per strain.
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Figure 3: Effect of leptin on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (A) and SHR (B). Effect of endothelial denudation on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (C) and SHR (D) in absence and presence of leptin. Data are shown in milligram as mean ± SEM of 10 animals per strain.

Mentions: After preincubation with leptin (10 nM), concentration-response curves to Ang II (10−10 to 10−6 M) were performed in aortic rings of both strains (Figure 3; Table 2). Leptin induced a significant reduction of Ang II-induced contractions in rings from WKY, whereas the effect of leptin was almost absent in rings from SHR (Figures 3A,B). The anticontractile effect of leptin was abolished in endothelium-denuded rings (Figures 3C,D).


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)

Effect of leptin on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (A) and SHR (B). Effect of endothelial denudation on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (C) and SHR (D) in absence and presence of leptin. Data are shown in milligram 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 3: Effect of leptin on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (A) and SHR (B). Effect of endothelial denudation on angiotensin II (Ang II)-induced contractions in aortic rings from WKY (C) and SHR (D) in absence and presence of leptin. Data are shown in milligram as mean ± SEM of 10 animals per strain.
Mentions: After preincubation with leptin (10 nM), concentration-response curves to Ang II (10−10 to 10−6 M) were performed in aortic rings of both strains (Figure 3; Table 2). Leptin induced a significant reduction of Ang II-induced contractions in rings from WKY, whereas the effect of leptin was almost absent in rings from SHR (Figures 3A,B). The anticontractile effect of leptin was abolished in endothelium-denuded rings (Figures 3C,D).

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