Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity

Abstract

To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p < 0.01 hypercaloric diet vs standard diet) in the presence of both prazosin and losartan but only in endothelium-intact vessels. Diet-induced obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p < 0.05 vs standard diet). Seven-week hypercaloric diet-induced obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice

“…Another interesting finding in the current study is the significant reduction of contractile responses to Phe detected in SOLF, UOLF, and HF mice, which has been previously described in mice fed a 62% fat HF diet for only 4 weeks [26]. This could be due to alterations in alpha-1 receptor function, as suggested by Juarez et al [41], though further studies are required to better address this matter. In contrast, a commercial diet providing 45% energy content from fat was not able to alter NA-induced contractions after even 32 weeks of dietary treatment [3], which evidences that the diets used in our study (which provide 62-70% energy from fat) are much more aggressive than 45% commercial HF diets.…”

C21 preserves endothelial function in the thoracic aorta from DIO mice: role for AT2, Mas and B2 receptors

“…Many reports have implicated the activation of the "deleterious arm" of the RAS in obesity-related endothelial dysfunction 26,27,34,35 . According to the conventional view of the RAS, the "protective arm" should be triggered in a pathological state such as obesity as a response to the negative effects driven by AT 1 R activation.…”