Proceedings of The Physiological Society

University of Edinburgh (2011) Proc Physiol Soc 25, C07 and PC07

Oral Communications

Adiponectin induces perivascular adipose tissue anticontractility in mouse mesenteric small arteries via activation of BKCa channels

F. M. Lynch1, Z. Yao1, S. B. Withers1, M. Werner1, A. M. Heagerty1

1. Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom.


Perivascular adipose tissue (PVAT) exerts an anticontractile effect on vascular tone which may provide protection against the development of hypertension. The factors responsible for this effect remain to be identified in this vascular bed. Adiponectin has been identified as responsible for anticontractility in human vessels, therefore the aim of this study was to determine if and how it is acting in the mouse mesenteric bed1. Male and female, C57BL/6 (Wild type (WT)), BKβ1-/- mice, Slo+/+ (WT) and slo-/- mice, (12-18 week old ~25g weight) were killed by stunning and cervical dislocation. Mesenteric arteries were mounted on a wire myograph. Cumulative concentration responses (10-9-10-5M) to norepinephrine (NE) were performed. Solution transfer experiments were performed. Solution was transferred from baths containing preconstricted (10-5M NE) WT PVAT arteries to WT and KO arteries lacking PVAT. In a second series of experiments cumulative concentration responses NE were performed before and after 45 minute incubation with adiponectin blocking peptide for PAb to adiponectin Receptor 1 (BPR1) (5μg/mL) (Enzo Life Sciences). Transfer of bath solution from preconstricted PVAT arteries to arteries without PVAT was also performed. Responses are expressed as mean (±SEM)% of KPSS constriction for cumulative concentration response curves and analysed using 2-way ANOVA or as mean change in tension(±SEM) and analysed using student’s t-test for transfer experiments. Responses to exogenous adiponectin (3μg/mL) were also assessed. Transfer of bath solution from preconstricted WT PVAT arteries to preconstricted (0.65±0.1mN/mm) WT arteries -PVAT (n=6) significantly reduced (P<0.05) tension (0.43±01mN/mm). However, transfer of solution from preconstricted WT PVAT arteries (n=6) to preconstricted (0.48±0.2mN/mm) BKβ1-/- arteries -PVAT did not significantly alter tension (0.56±0.3mN/mm). Transferral of solution from preconstricted WT PVAT arteries to preconstricted (0.25±0.1mN/mm) Slo+/+ arteries -PVAT (n=6) did not significantly alter tension (0.26±0.1mN/mm). PVAT (n=12) significantly (P<0.05) reduced tension (126.6±14.5%) produced by norepinephrine (10-6M) compared to that produced (98.4±7.7%) in the absence of PVAT (n=11). The presence of BPR1 abolished the anticontractile effect of PVAT; tension produced (113.6±12.9%) by PVAT arteries (n=8) was not significantly different from that produced (127.1±21.3%) by arteries without PVAT (n=5). Adiponectin produced significant (P<0.05) vasodilatation of preconstricted arteries (12.3±4.6%). These data suggest that adiponectin is the mediator of PVAT induced anticontractility and that it acts via AdipoR1. This acts via the BKCa channel.

Where applicable, experiments conform with Society ethical requirements