Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women.
OBJECTIVE
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW).


METHODS
In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography.


RESULTS
During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol.


CONCLUSIONS
Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.
Scuteri
Angelo
A
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, Maryland, USA. angeloelefante@interfree.it
Stuehlinger
Markus C
MC
Cooke
John P
JP
Wright
Jeanette G
JG
Lakatta
Edward G
EG
Anderson
David E
DE
Fleg
Jerome L
JL
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001916:Brachial Artery / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000097:blood*; D017698:Postmenopause / Q000378:metabolism*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D014664:Vasodilation / Q000502:physiology
D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine