Animal studies suggest that nitric oxide (NO) deficiency is linked to salt-
sensitive hypertension and that NO activity decreases during normal aging.
This study investigates the impact of increasing age and manipulations in d
ietary salt intake on biochemical indices of the NO system in healthy human
s, We measured NO2 + NO3 (NOx; stable oxidation products of NO) and cyclic
guanosine monophosphate (cGMP; major second messenger) in plasma and urine
of 30 healthy subjects aged 22 to 77 years. Subjects were maintained on con
trolled low NOx and low-, normal-, or high-salt diets for 3 days. Salt sens
itivity of blood pressure was seen only in the oldest subjects. plasma reni
n activity was suppressed by a high salt intake in all age groups, and base
line values declined with advancing age. Neither age nor salt intake correl
ated with indices of NO activity over the third 24-hour period of controlle
d salt intake. In a subgroup of subjects aged 33 +/- 4 years challenged wit
h ultrahigh sodium intake (400 mEq/24 h), again there was no increase in NO
2 + NO3 or cGMP measures. In contrast to animal studies, there is no correl
ation in humans between either salt intake or age and total NO production a
nd activity, indicated by NO2 + NO3 and cGMP measures. This does not preclu
de undetected alterations occurring in NO production and/or activity in str
ategic locations in the kidney and cardiovascular system. Limitations of bl
ood and urine measurements of NO2 + NO3 and cGMP as indices of NO activity
are discussed. (C) 2001 by the National Kidney Foundation, Inc.