Blood pressure variation in healthy humans: a possible interaction with beta-2 adrenergic receptor genotype and renal epithelial sodium channels.
Renal control of Na(+) regulation is a critical component to blood pressure regulation. It has recently been suggested that the beta-2 adrenergic receptor plays a role in blood pressure regulation possibly via renal epithelial sodium channels (ENaC). In the kidneys, gain of function mutations of the ENaC leads to increased salt-sensitivity and hypertension (Liddle's syndrome). In contrast, loss of function mutations of the ENaC leads to pseudohypoaldosteronism and is characterized by hypotension. Polymorphic variation of the beta-2 adrenergic receptor (beta2AR, the Arg16Gly polymorphism) leads to differences in physiologic function, in vivo. Specifically, subjects homozygous for Glycine at amino acid 16 have been shown to have enhanced forearm blood flow in response to isoproterenol and better airway function at baseline and during exercise when compared to subjects homozygous for Arginine at amino acid 16. We hypothesize, therefore, that subjects that are homozygous for Gly at amino acid 16 of the beta2AR have higher baseline blood pressure than Arg16 homozygotes due to beta2AR-mediated increases in ENaC activity in the kidney, caused, at least in part, by greater beta2AR density or enhanced beta2AR function of the Gly16 group.
Snyder
Eric M
EM
Division of Cardiovascular Diseases, Department of Internal Medicine, Gonda 5-369, Mayo Clinic and Foundation, 200 1st Street, SW, Rochester, MN 55905, USA.
Joyner
Michael J
MJ
Turner
Stephen T
ST
Johnson
Bruce D
BD
D000328:Adult; D001120:Arginine / Q000737:chemistry; D001794:Blood Pressure; D053503:Epithelial Sodium Channels; D005838:Genotype; D005998:Glycine / Q000737:chemistry; D006720:Homozygote; D006801:Humans; D007022:Hypotension; D007668:Kidney / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D009154:Mutation; D011110:Polymorphism, Genetic; D011650:Pulmonary Alveoli / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D018343:Receptors, Adrenergic, beta-2; D015222:Sodium Channels; D001120:Arginine; D005998:Glycine