Proceedings of The Physiological Society

University of Edinburgh (2011) Proc Physiol Soc 25, C20 and PC20

Oral Communications

Perivascular adipocyte induced anticontractility and adiponectin levels in type 1 diabetic rats

F. M. Lynch1, C. Withers1, A. Prosser1, R. Walker1, N. Gardener2, A. M. Heagerty1, S. B. Withers1

1. Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom. 2. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.


Vascular diseases such as microangiopathy represent the main cause of death in Type-1 diabetes. Although traditionally this is thought to be due in part to endothelial dysfunction, the role of perivascular adipose tissue (PVAT) has yet to be investigated. PVAT functions as an endocrine organ in its own right and provides an anticontractile effect in health to arteries due to release of various adipokines, including adiponectin. Although we have shown PVAT function is compromised in the metabolic syndrome, the effect in Type-1 diabetes however is unclear1. This study aims to examine arterial function in the presence and absence of PVAT in a rat model of type 1 diabetes and assess adiponectin levels in this model. Diabetes was induced in male Wistar rats (Charles River, UK) via intraperitoneal injection of freshly dissolved STZ (55mg/kg in sterile saline serum). Rats were humanely killed by cervical dislocation at 12 weeks. Age- and weight-matched rats were used as non-diabetic controls (group 1). A second control group of normal chow fed rats was also studied. Second order mesenteric arteries were dissected ± PVAT and studied using wire myography. Cumulative concentration responses (10-9-10-5M) to norepinephrine (NE) were performed. Responses are expressed as mean (±SEM)% of KPSS constriction (60mM) and analysed using 2-way ANOVA. Three different tissue samples were taken from each rat: adipose tissue (F), aorta (A), and mesenteric artery (M) for immunohistological analysis of adiponectin using a mouse anti-rat adiponectin antibody. Starting body weight of control animals was 358.4 ± 8.1g and of diabetic animals 357.3 ± 5.7g. At the end of the study control animals (group 1) significantly increased (P<0.05) body weight to 580.3 ± 15.8g compared with diabetic rats (382.2 ± 22.3g). Blood glucose of control groups was <6 mmol/L which was significantly less (P<0.05 t test) than that of the diabetic group (<27.4 mmol/L). PVAT induced an anticontractile effect (elicited by 10-6M NE) in normal chow fed controls (PVAT: 18 ± 3.7 % vs. no PVAT: 75.6 ± 8.0%; (n=36); P <0.05). The anticontractile effect was also present in weight-matched controls (PVAT: 8.9 ± 3.6% vs. no PVAT: 60.1 ± 13.9%; (n=6); P <0.05). However there was no significant difference in responses in the presence (42.3 ± 14.8%) or absence of PVAT (46.1 ± 10.8%) from arteries from diabetic rats (n=6). Immunohistochemistry indicated an increase in the expression of adiponectin in all three tissue samples (F, A and M) from diabetic rats compared with controls. These data demonstrate that diabetes inhibits the anticontractile effect of PVAT. This is accompanied with an increase in adiponectin levels. This is indicative of adiponectin resistance in these arteries and points to a pathological mechanism different to that seen in type 2 diabetes.

Where applicable, experiments conform with Society ethical requirements