Abstract 5039: Globular and Full-length Adiponectin Induce NO-Dependent Vasodilation in Resistance Arteries of ZL but Not ZDF Rats
Adiponectin increases NO-production in endothelial cell cultures and is reduced in the circulation of obese and diabetic patients, but it is not known whether adiponectin has a functional effect on small resistance arteries. In order to address this question, we assessed the direct vasodilatory response of mesenteric resistance arteries of Zucker diabetic fatty (ZDF) rat and the Zucker lean (ZL) rats to globular (gAd) and full-length adiponectin (fAd) in a small vessel myograph after precontraction with norepinephrine. Serum adiponectin levels measured by ELISA were significantly higher in ZL than in ZDF rats (ZL 4.0±0.1 μg/l vs ZDF 2.9±0.2 μg/l; p<0.001). Both gAd and fAd induced a relevant dose dependent vasodilation in ZL, but not ZDF rats (max. vasodilation to gAd: ZL 21.0±0.9% vs ZDF 2.9±0.9%; p<0.001. max. vasodilation to fAd: ZL 23.8±1.2% vs ZDF 1.4±1.1%; p<0.001). This vasodilatory effect in ZL rats could totally be blunted by preincubation with L-NAME (p<0.001) indicating that it is exclusively mediated by NO. ZDF rats showed a significantly lower endothelium-dependent vasodilation response to acetylcholine (max. vasodilation: ZL 96.7±5.5% vs ZDF 60.1±6.0%; p<0.001). The additional administration of low dose gAd or fAd could not improve the vasodilatory response to ACh. The gene expressions of AdipoR1 and AdipoR2 quantified by real-time RT-PCR were not significantly different in both animal models, AdipoR2 only tended to be higher expressed in ZDF rats (ZL 0.62±0.03 vs ZDF 0.68±0.06; p=0.061). But AdipoR1 was significantly more abundant expressed than AdipoR2 in resistance arteries of both ZL and ZDF rats (ZL: 1.06±0.04 vs 0.62±0.03; p<0.001. ZDF: 1.06±0.08 vs 0.68±0.06; p<0.001). In conclusion, we showed that adiponectin exerts a relevant NO-mediated vasodilation in resistance arteries of normal control rats. Reduced adiponectin serum levels and a blunted response to adiponectin in diabetic animals may contribute to endothelial dysfunction and thus play a role in the pathogenesis of atherosclerosis. In diabetes mellitus, adiponectin receptors are not downregulated in resistance arteries indicating a dysfunction downstream of the receptors.