Premium
Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide
Author(s) -
Gao YJ,
Lu C,
Su LY,
Sharma A M,
Lee R M K W
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707228
Subject(s) - phenylephrine , contraction (grammar) , chemistry , nitric oxide , endocrinology , endothelium , vasodilation , medicine , organic chemistry , blood pressure
Background and purpose: Perivascular adipose tissue (PVAT) attenuates vascular contraction, but the mechanisms remain largely unknown. The possible involvement of endothelium (E) and hydrogen peroxide (H 2 O 2 ) was investigated. Experimental approach: Aortic rings from Wistar rats were prepared with both PVAT and E intact (PVAT+E+), with either PVAT or E removed (PVAT‐E+, or PVAT+E‐), or with both removed (PVAT‐E‐) for functional studies. Nitric oxide (NO) production was measured. Key results: Contraction to phenylephrine and 5‐HT respectively was highest in PVAT‐E‐, lowest in PVAT+E+, and intermediate in PVAT+E‐ or PVAT‐E+. In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring (donor) to a PVAT‐ ring (recipient) induced relaxation in the recipient. This relaxation was abolished by E removal, NO synthase inhibition, scavenging of NO, high extracellular K + , or blockade of calcium‐dependent K + channels (K Ca ). The solution stimulated NO production in isolated endothelial cells and in PVAT‐E+ rings. In E‐ rings, the contraction to phenylephrine of PVAT+ rings but not PVAT‐ rings was enhanced by catalase or soluble guanylyl cyclase (sGC) inhibitor, but reduced by superoxide dismutase and tiron. In PVAT‐E‐ rings, H 2 O 2 attenuated phenylephrine‐induced contraction. This effect was counteracted by sGC inhibition. NO donor and H 2 O 2 exhibited additive inhibition of the contraction to phenylephrine in PVAT‐E‐ rings. Conclusion: PVAT exerts its anti‐contractile effects through two distinct mechanisms: (1) by releasing a transferable relaxing factor which induces endothelium‐dependent relaxation through NO release and subsequent K Ca channel activation, and (2) by an endothelium‐independent mechanism involving H 2 O 2 and subsequent activation of sGC. British Journal of Pharmacology (2007) 151 , 323–331; doi: 10.1038/sj.bjp.0707228