Effects of aging and alterations in dietary sodium intake on total nitric oxide production

Abstract

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 dietary salt intake on biochemical indices of the NO system in healthy humans. We measured NO 2 + NO 3 (NO X ; 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 controlled low NO X and low-, normal-, or high-salt diets for 3 days. Salt sensitivity of blood pressure was seen only in the oldest subjects. Plasma renin activity was suppressed by a high salt intake in all age groups, and baseline values declined with advancing age. Neither age nor salt intake correlated with indices of NO activity over the third 24-hour period of controlled salt intake. In a subgroup of subjects aged 33 ± 4 years challenged with ultrahigh sodium intake (400 mEq/24 h), again there was no increase in NO 2 + NO 3 or cGMP measures. In contrast to animal studies, there is no correlation in humans between either salt intake or age and total NO production and activity, indicated by NO 2 + NO 3 and cGMP measures. This does not preclude undetected alterations occurring in NO production and/or activity in strategic locations in the kidney and cardiovascular system. Limitations of blood and urine measurements of NO 2 + NO 3 and cGMP as indices of NO activity are discussed. Index WordsSodium excretion; blood pressure (BP); salt-sensitive hypertension; cyclic guanosine monophosphate (cGMP); NO 2 + NO 3 (NO X ); nitric oxide (NO) With Advancing Age, the kidney is less able to either conserve sodium in response to dietary restriction or remove sodium after excess intake. 1,2 Both aging rats and humans have a blunted ability to excrete an acutely administered sodium load, 1,3,4 and pressure natriuresis is attenuated in the old rat. 5,6 According to Guyton et al, 7 impaired pressure natriuresis leads to salt-sensitive hypertension, and the incidence of salt-sensitive hypertension increases substantially in humans with increasing age, 8 reflected by an increased frequency of low-renin essential hypertension. 9 Increased nitric oxide (NO) production occurs in response to high dietary salt intake in normal rats, and chronic NO synthase (NOS) inhibition combined with high dietary salt intake can lead to volume-dependent hypertension. [10][11][12][13] In addition, the genetically salt-sensitive hypertension in the Dahl rat is associated with defective NO production in the face of high sodium intake. 14,15 NO directly inhibits sodium transport in several parts of the tubule. NO is NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript also a powerful renal vasodilator, and in NO deficiency experimentally induced by NOS inhibition, pressure natriuresis is attenuated. 16,17 It therefore is widely held that an appropriate increase in NO production in the kidney and perip...

Changes in renal hemodynamics and structure in the aging kidney; sexual dimorphism and the nitric oxide system

“…There is clear evidence that U NO x V falls in the aging (male) rat (Reckelhoff et al, 1994;Sonaka et al, 1990;Hill et al, 1997;Erdely et al, 2003), denoting a reduction in total NO production. In man, we were unable to document a fall in U NO x V with age (Schmidt et al, 2001) although Lyons et al (1997) did report reductions in U NO x V in healthy old age. There is clearly a reduction in endothelial NO activity with age, leading to endothelial dysfunction.…”

Cisplatin nephrotoxicity aggravated by cardiovascular disease and diabetes in lung cancer patients

“…SILVA [9] suggested that ageing should be seen as the erosion of generous spare capacity or loss of renal safety margins. The tubular systems becomes less capable of conserving or excreting NaCl [14]. Among the elderly, exsiccation and/or hyponatraemia becomes prevalent [15].…”

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

“…Dietary calcium reduces blood pressure by stabilizing the arterial membranes, blocking its own entry into the cell, inhibiting contraction of arterial smooth muscles and by enhancing NO synthesis (Passmore et al, 1997;Das, 2001a). Conversely, high salt intake reduces NO synthesis, although this action has been disputed (Schmidt et al, 2001). High salt intake initially stimulates NO production (to maintain normotension despite increase in blood volume caused by increased salt intake) to maintain blood flow, and only when the enhanced salt intake continues for a long time, NO synthesis is decreased (possibly because of the exhaustion of the eNOS activity), which leads to the development of hypertension (Nakanishi et al, 2002).…”