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¹ Department of Anaesthesiology
² Department of Biostatistics
³ Division of Cardiovascular Diseases, Department of Internal Medicine
⁴ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

Dietary Na⁺ intake influences ß₂-adrenergic receptor (ß₂AR) responsiveness. While receiving a normal Na⁺ diet (150 mmol day^–1), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm ß₂AR-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 ß₂AR-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 ß₂AR 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.

(Received 21 April 2006; accepted after revision 31 May 2006; first published online 1 June 2006)
Corresponding author John H. Eisenach: Anesthesia Research, Mayo Clinic and Foundation, 200 1st Street, SW Rochester, MN 55905, USA. Email: eisenach.john{at}mayo.edu

This article has been cited by other articles:

				E. M. Snyder, S. T. Turner, M. J. Joyner, J. H. Eisenach, and B. D. Johnson The Arg16Gly polymorphism of the {beta}2-adrenergic receptor and the natriuretic response to rapid saline infusion in humans J. Physiol., August 1, 2006; 574(3): 947 - 954. [Abstract] [Full Text] [PDF]