The Influence of β1‐Adrenergic Receptor Genotype of Renal Sodium Handling and Blood Pressure Response to Angiotensin Receptor Blockers in Hypertension Patients

Abstract

IntroductionThe β1‐adrenergic receptors (ADRB1) are found primarily in the heart and the juxtaglomerular cells of the kidneys. Within the kidneys, ADRB1 promote the release of renin and the activation of the renin‐angiotensin‐aldosterone system (RAAS). The RAAS plays a primary role in the regulation of renal Na+ handling and blood pressure (BP). Specifically, within the RAAS, aldosterone preferentially increases renal tubular luminal Na+ transport via increasing apical Na+ permeability. As a result, systolic and diastolic blood pressures are impacted by RAAS activity. Additionally, baseline renin levels predict Na+ sensitivity. Multiple polymorphisms of the ADRB1 have been identified as including a glycine (Gly) for arginine (Arg) substitution at amino acid 389. The Gly389 polymorphism is associated with a lower risk of hypertension and increased plasma renin levels compared to the Arg389 polymorphism. The influence of ADRB1 genotype on renin release and blood pressure suggests the functional role it may play in renal Na+ handling.PurposeThe purpose of this study was to identify the influence of ADRB1 genotype on renal Na+ handling and response to angiotensin receptor blocker (ARB) therapy in hypertension patients.Methods158 patients with controlled hypertension on a prescribed ARB completed one study visit consisting of a buccal swab collection and a medical chart review for objective BP history. Buccal swabs were analyzed for ADRB1 389 genotype (Gly389Gly = 14, Gly389Arg = 69, and Arg389Arg = 75). The relationship between genotype and Δ systolic blood pressure (SBP), Δ diastolic blood pressure (DBP), Δ mean arterial blood pressure (MAP), and the average SBP, DBP, and MAP for the last year was assessed.ResultsThere were no differences between genotype groups for age, height, weight, or BMI. There were no differences between genotype groups for ΔSBP, ΔDBP, ΔMAP (ΔSBP = −29.29 ± 2.91, −34.36 ± 3.59, −32.30 ± 3.21, ΔDBP = −16.43 ± 2.48, −11.89 ± 3.84, −13.71 ± 2.72, ΔMAP = −20.71 ± 2.22, −16.91 ± 3.71, −16.83 ± 2.81 for Gly389Gly, Gly389Arg, and Arg389Arg respectively). Additionally, there was no differences in one‐year average for DBP and MAP (DBP = 79.17 ± 2.65, 77.97 ± 0.99, 76.98 ± 0.93, MAP = 98.22 ± 2.85, 94.12 ± 0.93, 94.32 ± 0.83 for Gly389Gly, Gly389Arg, and Arg389Arg respectively). There was a statistically significant difference in one‐year average for SBP between genotype groups (136.32 ± 3.62, 126.67 ± 1.35, 128.98 ± 1.15 for Gly389Gly, Gly389Arg, and Arg389Arg respectively)ConclusionsThe present study suggests ADRB1 389 genotype influences BP response to ARB therapy in hypertension patients, particularly the one‐year average of SBP.Support or Funding InformationGeneticure Inc.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.