Dietary sodium restriction and β₂‐adrenergic receptor polymorphism modulate cardiovascular function in humans

Abstract

Dietary Na + intake influences β 2 -adrenergic receptor (β 2 AR) responsiveness. While receiving a normal Na + diet (150 mmol day -1 ), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm β 2 AR-mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na + restriction eliminates genotype differences in forearm and systemic β 2 AR-mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na + intake (10 mmol day -1 ) in healthy Gly16 (n = 17; age, 31 ± 7 year) and Arg16 homozygotes (n = 15; age, 29 ± 8 year). After the low-Na + diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with N G -mono-methyl-L-arginine (L-NMMA). In the Gly16 group, the low-Na + diet decreased baseline CO from 6.4 ± 1.4 to 5.5 ± 1.2 l min -1 (P = 0.003, paired t test), tended to decrease stroke volume from 97.0 ± 20.6 to 86.9 ± 21.7 ml (P = 0.06) and increased peripheral resistance from 1106 ± 246 to 1246 ± 222 dynes s cm -5 (P = 0.02); significant effects of the low-Na + diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremenetal doses of isoprenaline did not differ between genotype groups before or after administration of L-NMMA. We conclude that dietary Na + restriction blunted the increased forearm NO-mediated β 2 AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na + intake, while baseline CO decreased and peripheral resistance increased in this group. This study provides evidence that dietary Na + modulates effects of the Arg16Gly polymorphism on cardiovascular function.

Genetic Influences of .BETA.-Adrenoceptor Polymorphisms on Arterial Functional Changes and Cardiac Remodeling in Hypertensive Patients

“…In another study, the Gly16 and Glu27 polymorphisms in the β 2 ADR were associated with sympathetic overactivity, as reflected by high plasma norepinephrine levels ( 33 ). In a study by Eisenach et al ., dietary sodium restriction blunted the increase in nitric oxide-mediated, β 2 ADR responsiveness in Gly16 homozygotes of the forearm following administration of normal dietary sodium, while baseline CO decreased and peripheral resistance were increased by the sodium restriction (34). In male twins with highly similar genetic and environmental backgrounds, the Arg64 variant of the β3ADR polymorphism was found to be associated with insulin resistance and higher post-prandial hyperglycemia (35).…”

β-Adrenergic receptor gene polymorphism is a genetic risk factor for cardiovascular disease: a cohort study with hypertensive patients

“…18 Dietary sodium restriction blunts the increase in nitric oxide-mediated b 2 ADR responsiveness of the forearm in Gly16 homozygotes following administration of normal dietary sodium, whereas baseline cardiac output decreases and peripheral resistance increases under sodium restriction. 19 In male twins with highly similar genetic and environmental backgrounds, the Arg64 variant of the b 3 ADR polymorphism was found to be associated with insulin resistance and higher post-prandial hyperglycemia. 20 As we noted in the introduction, many cross-sectional studies have focused on cardiovascular-related disease and these SNPs of the bADRs.…”

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

“…To address this limitation, we infused isoproterenol relative to lean forearm mass and compared vasodilator responses to the same relative ␤-adrenoceptor stimulus between groups. This methodology is widely accepted (10,11,17).…”

“…Isoproterenol (isoproterenol hydrochloride injection; Marathon Pharmaceuticals) was infused at four separate doses (1,3,6, and 12 ng·100 g Ϫ1 ·min Ϫ1 ), similar to those published previously (10,11,17). N G -monomethyl-L-arginine (L-NMMA; acetate; Clinalfa BaChem) was infused at a rate of 10 mg/min over 5 min, followed by a 1 mg/min maintenance dose (5,7,21).…”