A17398 Nitric oxide synthase regulates of the anti-contractile functions of perivascular adipose tissue

Abstract

Objectives: Perivascular adipose tissue (PVAT) plays a crucial role in the modulation of vascular tone. Loss of function in obesity leads to an increase in arterial tone, and may contribute to development of hypertension. Activation of nitric oxide synthase (NOS) has been implicated in the anti-contractile effect of PVAT. Accordingly, we have examined the roles of NOS in healthy and obese PVAT. Methods: Electrical field stimulation profiles or noradrenaline concentration response curves were generated in healthy, obese, and eNOS−/− mouse mesenteric resistance arteries. Pharmacological manipulation of NOS was conducted using the non-specific inhibitor; L-NMMA, and activator; histamine. The role of β3-adrenoceptors was investigated using the agonist CL-316,243. Immunohistochemistry was use to examine expression of the endothelial NOS isoform (eNOS) in PVAT. Results: Stimulation of PVAT induced an anti-contractile effect on healthy mouse arteries, which was absent in obese and eNOS−/− mouse arteries. Inhibition of NOS in healthy mouse PVAT abolished the anti-contractile effect, and activation of NOS in obese PVAT restored the anti-contractile effect. Using immunohistochemistry, eNOS is the isoform present in mesenteric PVAT, and expression is unchanged in obesity. The β3-adrenoceptor agonist enhanced the anti-contractile effect, and this enhancement was abolished using the NOS inhibitor. Conclusion: These results demonstrate that the β3-adrenoceptor mediated anti-contractile effect of PVAT is dependent upon NOS. In obesity, the anti-contractile effect is lost which may contribute to development of hypertension. However, function can be rescued using activation of NOS; presenting a potential pharmacological target for intervention in obesity-related hypertension.