Proceedings of The Physiological Society
University of Edinburgh (2011) Proc Physiol Soc 25, C05 and PC05
The effect of hypoxia and perivascular fat on potassium channels in mice mesenteric arteries
Z. Yao1, F. Lynch1, A. M. Heagerty1
1. Cardiovascular Reserach Group, University of Manchester, Manchester, United Kingdom.
Previously studies demonstrated that perivascular adipose tissue (PVAT) releases adipoycyte-derived relaxing factors (ADRF) which reduces vascular contractility (1). The study explores the potential influences of hypoxia on PVAT and potassium channels in isolated mice mesenteric arteries. Male and female, -/-BKβ1 (large-conductance Ca2+ activated potassium (BKCa) channel knockout), C57BL/6 (Wild type) mice (12-18 week old ~25g weight) were killed by stunning and cervical dislocation. Mesenteric arteries with or without PVAT were mounted on a wire myograph for isometric tension recording. Cumulative concentration responses (10-9-10-5M) to norepinephrine (NE) were performed before and after 2.5 hours hypoxia (95%N2, 5%CO2), in the presence or absence of ATP-sensitive potassium channel (KATP) blocker glibenclamide (10µM). Responses are expressed as mean (±SEM) % of KPSS constriction and analysed using 2-way ANOVA. NE produced a concentration dependent constriction of arteries. PVAT significantly (P<0.01) reduced this constriction in wild-type vessels (Figure A). Hypoxia significantly enhanced (P<0.001) vasorelaxation effect of adipose tissue (n=4, 54.4±11.4%vs21.1±8.9%), while no vasorelaxation effect was observed in the arteries without adipose tissue (n=4, 85.3±12.4%vs81.3±18.5%). In the -/-BKβ1 group hypoxia had no significant effect on the contractility between the non-PVAT and PVAT vessels (n=5, 58.23±11.5%vs46.85±22.5%). Glibenclamide significantly (p<0.01) impaired the hypoxic vasorelaxation effect of PVAT in wild-type arteries (n=4, 72.1±21.3%vs138.0±55.4%). Glibenclamide does not affect the contractile responses of vessels in normoxic conditions (n=6, 84.0±26.1%vs51.4±15.2%). In arteries from -/-BKβ1 mice, glibenclamide does not significantly affect the contractile response of PVAT vessels to NE compared with the corresponding control responses irrespective of hypoxic (n=4, 46.9±22.5%vs33.6±13.7%) and normoxic (n=5, 37.7±11.6%vs40.3±16.0%) conditions. Our findings indicate that hypoxia has a vasorelaxation effect on mice mesenteric arteries and it is dependent on the presence of intact PVAT. In addition, activation of BKCa and KATP channels plays an important role in this response.
Where applicable, experiments conform with Society ethical requirements