Abstract 13047: The Modulatory Effects of Perivascular Adipose Tissue on the Renal Arterial Vasorelaxation and Its Relationship With Kidney Function in Metabolic Syndrome

Abstract

Metabolic syndrome (MetS) is a cluster condition that increases the risk of cardiovascular diseases and type 2 diabetes. Perivascular adipose tissue (PVAT) regulates the arterial tone. We have demonstrated that the renal arterial PVAT enhances the vasorelaxation response in MetS model strains, SHRSP.Z- Lepr fa /IzmDmcr rats (SPZF) and SHR/NDmcr-cp rats (CP). Furthermore, we have found that overactivation of angiotensin II type 1 receptor (AT1R) signaling and a decrease in apelin levels in PVAT leads to a decline in compensatory PVAT effects. MetS is associated with chronic kidney disease, and the dysfunction of the PVAT favoring the vasorelaxation response could be a reason for kidney disease development. Therefore, we investigated the relationship between PVAT function and kidney function using MetS model rats.Renal arteries were isolated from the male and female SPZF and CP at 23 weeks of age. Vasorelaxation and mRNA transcript levels in PVAT were examined using organ bath methods and quantitative real-time polymerase chain reaction, respectively. Systolic blood pressure (sBP) was measured using a tail-cuff method. Insulin, glucose, and creatinine in the serum and protein in the urine were measured using commercial kits and eGFR, and the HOMA-IR were calculated.sBP was higher in SPZF than CP, but lower in females than males. HOMA-IR and urine protein levels were the lowest, while eGFR and enhancing effects of PVAT on acetylcholine-induced relaxations were the highest in female CP among the groups. eGFR was negatively correlated with sBP, HOMA-IR, and urinary protein levels. The enhancements of relaxations by PVAT were negatively correlated with sBP, HOMA-IR, and AT1R activity in PVAT.This study suggests that the insulin resistance and high blood pressure are associated with PVAT dysfunction, resulting from AT1 activation in PVAT, while it does not support the hypothesis that the disappearance of the effects of PVAT directly leads to kidney dysfunction.