Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension.
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.
Instituto Pluridisciplinar, Facultad de Farmacia, Universidad Complutense de Madrid Madrid, Spain.
Beatriz
B
Gálvez-Prieto
Beatriz
B
Somoza
Marta
M
Gil-Ortega
Concha F
CF
García-Prieto
Ana I
AI
de Las Heras
M Carmen
MC
González
Silvia
S
Arribas
Isabel
I
Aranguez
Juliane
J
Bolbrinker
Reinhold
R
Kreutz
Mariano
M
Ruiz-Gayo
Maria S
MS
Fernández-Alfonso