Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC187
The effects of hypoxia and eplerenone on perivascular adipose tissue-induced anticontractility in isolated mesenteric arteries; role of BKCa channels.
F. Lynch1, S. B. Withers1, M. Werner1, A. M. Heagerty1
1. Cardiovascular Research, Biomedicine, University of Manchester, Manchester, United Kingdom.
There is increasing interest in how perivascular fat (PVAT) favourably influences tone by producing an anticontractile effect. We have shown that this effect is mediated by BKCa channels. This study examines the effects of hypoxia on contractility and role of BKCa channel in mediating this response. The effect of eplerenone on this response was also examined Mesenteric arteries from Slo+/+ (wild type) and Slo-/- (BKCa knockout) mice were dissected ± PVAT and were mounted on a wire myograph. Cumulative concentration responses (10-9-10-5M) to norepinephrine (NA) were performed before and after 2.5hr hypoxia (N2/95%CO2) ± eplerenone (5μM). Responses are expressed as mean (±SEM) % of KPSS constriction and analysed using 2-way ANOVA. In +PVAT arteries (n=16) from Slo+/+ animals, constriction (94(12) % at 3x10-6M NA) was significantly less (P<0.05) than that produced in -PVAT arteries (142(27) % at 3x10-6M NA). Hypoxia significantly (P<0.05) reduced tension compared with vessels from wild type animals. Tension (n=8) in +PVAT arteries (31(11) % at 3x10-6M NA) was significantly (P<0.05) less than that (91(36) % at 3x10-6M NA) in -PVAT arteries (n=7). Eplerenone reversed this in (n=6) +PVAT arteries (98(21) % at 3x10-6M NA) but not in (n=7) -PVAT arteries (75(23) % at 3x10-6M NA). In arteries from Slo-/- mice, there was no significant difference in response to NA (n=12) in +PVAT (103(23) % at 3x10-6M NA) arteries and (n=13) - PVAT arteries (110(36) % at 3x10-6M NA). Hypoxia did not significantly alter vasoconstriction in (n=7) +PVAT arteries (74(9) % at 3x 10-6M NA) or (n=8) -PVAT arteries (119(40) % at 3x10-6M NA). Eplerenone did not alter contractility (n=7) +PVAT arteries (104(24) % at 3x10-6M NA) or (n=8) -PVAT arteries (105 (35) % at 3x10-6M NA). These results suggest that hypoxia reduces constriction in arteries from Slo+/+ mice and this effect is greater effect in arteries with PVAT. This is reversed by eplerenone. The absence of hypoxic dilation in arteries lacking BKCa channels suggest that they play a vital role in this effect.
Where applicable, experiments conform with Society ethical requirements