Nebivolol restores the anticontractile effect of mesenteric perivascular adipose tissue lost due to obesity.

Obesity is associated with arterial hypertension and vascular dysfunction, characterized by the loss of the anticontractile effect of perivascular adipose tissue (PVAT). In obesity, the PVAT exhibits a pro-oxidative and pro-inflammatory phenotype, leading to vascular hypercontractility. The anti-hypertensive nebivolol is a selective β1-adrenoreceptor antagonist known to display additional actions, such as β3-adrenoreceptor activation and antioxidant effects. We hypothesized that nebivolol would restore both the increase in blood pressure and the loss of the anticontractile effect of PVAT induced by obesity. With this purpose, male Wistar Hannover rats were treated with a high-calorie diet for 14 weeks. From weeks 10-14, the rats received a daily dose of nebivolol (10 mg/kg, via gavage). Obesity leads to increased blood pressure and hypercontractility in mesenteric arteries, particularly in the presence of PVAT. However, treatment with nebivolol reversed these responses. We observed an increased presence of macrophages in the mesenteric PVAT (mPVAT) of obese rats, while mesenteric arteries showed no such increase. This response was accompanied by elevated levels of superoxide (O2•-), TNF-α, IL-6, IL-1β, and leptin. In contrast, obesity decreased the levels of nitric oxide (NO) and adiponectin within the mPVAT. Nebivolol treatment effectively reversed these obesity-induced changes in pro-inflammatory parameters and vasorelaxant factors derived from mPVAT. Overall, our results revealed that nebivolol reversed the obesity-induced loss of the anticontractile effect of the mPVAT by promoting antioxidant and anti-inflammatory effects. Hence, nebivolol represents a powerful pharmacological tool in addressing cardiovascular dysfunctions induced by obesity.