Decreased alpha 2B adrenergic receptor expression increases vascular but decreases renal eNOS expression.

Abstract

Previous studies in mesenteric arteries from mice null for the a2B adrenergic receptor gene (a2B‐AR) suggest decreased a2B‐AR expression is associated with increased endothelial nitric oxide synthase (eNOS) expression in mesenteric arteries. Other studies have shown heterozygous a2B‐AR knockouts (HET) are less susceptible to renal hypertension than wildtype (WT) mice suggesting the HET genotype can be protective from some types of cardiovascular disease. Therefore we hypothesized a2B‐AR inhibit the expression of eNOS in other organs including the aorta, heart and kidney. Opposite to our prediction, western blots demonstrated a tendency for decreased eNOS protein expression in heart, aorta and renal medulla from HET mice and significantly lower expression in renal cortex (WT=1.0±0.1 vs HET=0.54±0.1 densitometry units, p<0.05). The renal medulla (WT=1.21±0.08 vs HET=0.84±0.05, p<0.05) and renal cortex (WT=1.06±0.05 vs HET=0.91±0.06, p<0.05) from HET mice also had decreased eNOS mRNA expression compared to WT. These results suggest α2B‐AR do not directly regulate eNOS expression but indirect effects of lower α2B‐AR expression lead to increased eNOS in small arteries and decreased eNOS in other tissues. The significance of decreased eNOS expression in the kidney on the altered blood pressure regulation in these mice remains to be investigated.