OR11-04 Effects Of β2-adrenergic Receptor Diplotype Onsalt Sensitive Blood Pressure, Aldosterone Secretion, And Renal Blood Flow

Abstract Disclosure: E. Caliskan Guzelce: None. M. heydarpour: None. L. Pojoga: None. G.H. Williams: None. Background: Genetic variation in the β2-Adrenergic Receptor (ADRB2) may influence blood pressure regulation, aldosterone secretion, and renal hemodynamics. This study investigated the impact of ADRB2 diplotype on salt-sensitive blood pressure (SSBP), aldosterone (ALDO), and renal blood flow (RBF) in a diverse cohort of 517 individuals, stratified by age, sex, and disease status. Methods: Participants from HyperPath study cohort were grouped into homozygous risk, heterozygous risk, and homozygous non-risk diplotype groups. We assessed SSBP, ALDO levels, and RBF under liberal and restricted salt diets. Subgroup analyses were performed in younger (<51 years) and older (≥51 years) individuals, as well as by hypertensive and normotensive status. Results: Across the full cohort, SSBP was associated with age, sex, and disease status (p < 0.001 for each), but not with diplotype alone. In participants younger than 51 years (N = 333), SSBP was significantly higher in homozygous risk individuals than heterozygous risk, and homozygous non-risk diplotype groups (p = 0.01, and p=0.007, res.), particularly among hypertensives (p=0.025). In contrast, SSBP did not differ among diplotype groups in older individuals or normotensives. Baseline aldosterone on a liberal salt diet was elevated in the risk diplotype group in both hypertensive and normotensive young individuals (p = 0.02, p=0.03, res.), but not on a restricted salt diet. RBF was significantly higher in the homozygous risk diplotype group under both salt conditions in the young cohort (p = 0.02, p=0.01, res.). However, when stratified by disease state, RBF was significantly higher in the homozygous risk diplotype group in young normotensives (p = 0.03), but not in young hypertensives. No significant differences were observed in plasma renin activity or urinary aldosterone excretion across diplotype groups. Sex did not modify SSBP response within the young cohort. Conclusions: ADRB2 diplotype influences aldosterone secretion and renal blood flow, particularly in younger individuals. While genotype-related differences in SSBP were evident only in young hypertensives, elevated aldosterone levels and increased renal blood flow were also observed in normotensives. This suggests that enhanced renal perfusion may buffer the pressor effects of aldosterone in young normotensives, but not in hypertensives, pointing to early genotype-driven physiological adaptations that may precede the development of overt hypertension. Presentation: Saturday, July 12, 2025