Nitric oxide production decreases after salt loading but is not related to blood pressure changes or nitric oxide-mediated vascular responses.
BACKGROUND
Nitric oxide production is a homeostatic mechanism that may regulate blood pressure during salt loading. Salt-sensitive hypertension in animal models and in humans is characterized by increased blood pressure and decreased nitric oxide production after salt loading. It is not known if this impaired nitric oxide production is the result of hypertension or is a mechanism contributing to the blood pressure response to salt.


RESULTS
The effects of salt loading on blood pressure, nitric oxide-mediated vasodilation and nitric oxide production were measured in 25 normotensive subjects after 6 days on either a high (400 mmol/day) or low (10 mmol/day) sodium, low nitrate diet. Mean arterial pressure increased during the high-salt diet [4 +/- 1 mmHg (mean +/- SEM)] in 12 subjects and remained unchanged or decreased (-4 +/- 1 mmHg) in 13 subjects. Plasma nitrite and nitrate, a measure of nitric oxide production, decreased significantly from 39 +/- 3.3 micromol/l during the low-salt diet to 22.4 +/- 2.4 micromol/l during the high-salt diet (P = 0.0001). However, changes in mean arterial pressure from low- to high-salt diet did not correlate with changes in plasma nitrite and nitrate (r = 0.14, P = 0.51). Forearm blood flow increased significantly (P <0.0001) in response to mental stress, a nitric oxide-mediated response, but was not affected by sodium intake (from 7.8 +/- 0.9 to 11.2 +/- 1.4 ml/min per 100 ml during low salt versus 8.5 +/- 1.2 to 10.4 +/- 1.3 ml/min per 100 ml during high salt,P = 0.3).


CONCLUSIONS
Salt loading results in a decrease in nitric oxide production in both salt-sensitive and salt-resistant normotensive subjects, which is independent of changes in blood pressure and does not affect the nitric oxide-mediated vascular response to mental stress. In contrast to salt-resistant animal models, salt loading in healthy subjects does not increase nitric oxide production. Therefore, the increased blood pressure response to salt loading may occur through mechanisms other than nitric oxide, or salt-sensitive individuals are more sensitive to the reduced nitric oxide production that occurs after salt loading in both salt-sensitive and salt-resistant subjects.
Dishy
Victor
V
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6202, USA.
Sofowora
Gbenga G
GG
Imamura
Hitoshi
H
Nishimi
Yukihide
Y
Xie
Hong-Guang
HG
Wood
Alastair J
AJ
Stein
C Michael
CM
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D012016:Reference Values; D012039:Regional Blood Flow; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology*
D009566:Nitrates; D009573:Nitrites; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide