DIABETES IMPAIRS PERIVASCULAR ADIPOSE TISSUE (PVAT)-MEDIATED VASCULAR RESPONSES IN RAT MESENTERIC AND ILIAC ARTERIES

Abstract

Objective: To study the role of PVAT in vascular function of blood vessels from hypertensive and diabetic rats. Design and method: Mesenteric and iliac artery rings were isolated ± PVAT from Sprague Dawley (SD), and diabetic and non-diabetic TGR (mREN2)27 (REN2) rats. Vascular activity was measured in organ baths by constructing concentration-response curves to endothelin (ET-1) or acetylcholine (ACh). To assess the involvement of NO and endothelium-dependent hyperpolarization (EDH) pathways, ACh effects were studied with the NO synthase inhibitor L-NAME and/or the EDH inhibitors apamine+TRAM-34. ET-1 effects were additionally studied in the presence of the endothelin type A and type B receptor (ETAR, ETBR) blockers BQ123 and BQ788. Constrictor data are expressed as a % of the response to 100 mmol/L K+, and dilator effects as a % of the preconstriction to the thromboxane A2 agonist U46619. Results: With PVAT, ET-1 constricted SD and REN2 iliac arteries identically (Emax 126±28 and 119±48, pEC50 7.68±0.29 and 7.59±0.35). BQ788 potentiated constriction, while BQ123 prevented it. Without PVAT, BQ788 had potentiating effect, while BQ123 exerted blockade. Indicating that acute ETBR stimulation results in PVAT-dependent vasodilation. DM reduced the effect of ET-1 in PVAT+ vessels (Emax 78±56, pEC50 6.36±2.59). Yet, PVAT removal restored the ET-1 effect to normal, while BQ788 was still without effect, and BQ123 exerted its usual blockade. This indicates that in DM, PVAT continuously releases relaxant factors that counteract ET-1-mediated effects, even without ETBR stimulation. ACh relaxed PVAT+ SD and REN2 mesenteric arteries identically (Emax 85±15 and 81±16, pEC50 5.70±0.79 and 6.43±0.61), additionally L-NAME blocked was comparable, while EDH blockade had no effect. PVAT removal did not alter ACh responses, and L-NAME and EDH inhibition yielded an identical degree of blockade, with additive effects. This indicates that PVAT counteracts EDH-mediated responses. DM did not alter the response to ACh, but under DM conditions, EDH inhibition yielded blockade in the presence of PVAT, this effect was additive to that of L-NAME. Thus, DM diminishes the anti-EDH effects of PVAT. Conclusions: PVAT releases both relaxant and contractile factors that affect vascular reactivity, and DM impairs PVAT function.