Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans

Bech, Jesper N.; Nielsen, C. B.; Ivarsen, Per; Jensen, Kimmo; Pedersen, E. B.

doi:10.1152/ajprenal.1998.274.5.f914

Cited by 49 publications

(56 citation statements)

References 24 publications

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Section: Nih-pa Author Manuscriptsupporting

confidence: 57%

“…A high-salt diet produced an impressive amplification of the pressor, renal vasoconstrictor, and antinatriuretic effects of acute NOS inhibition in healthy humans, suggesting that NO activity increases in the kidney and peripheral vasculature under conditions of sodium loading. 34 Unfortunately, the present study supports the notion that even measured under optimal conditions, simple plasma and urine analyses of NO X and cGMP are not reliable indices of renal or vascular NO activity.The primary goal of our experiments is to investigate the activity of the NO system in healthy aging humans. Based on animal studies, 18-20 we had anticipated that baseline total NO production would decrease with advancing age, and in addition, the ability of a high salt intake to increase NO production would be attenuated with aging.…”

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

Schmidt

Beierwaltes

Baylis

2001

American Journal of Kidney Diseases

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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...

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Section: Nih-pa Author Manuscriptsupporting

confidence: 57%

supporting

confidence: 57%

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

Schmidt

Beierwaltes

Baylis

2001

American Journal of Kidney Diseases

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“…7 NO diffuses into vascular smooth muscle cells, where it activates soluble guanylate cyclase to form cGMP, 21 which normally determines a state of relaxed arteriolar tone and vasodilatation in humans. 22 In healthy humans 23 and SDs, 24 NaCl loading induces a robust increase of NOS activity, as judged by the increase in apparent rates of formation of NO and cGMP. There is substantial evidence that an L-arginine-reversible inhibition of NOS is critical to the causation of the pressor effect induced by NaCl loading in both DSs, 25 and in DRs and SDs rendered SS by L-arginine analogues.…”

Section: Discussionmentioning

confidence: 99%

Salt Sensitivity in Blacks

et al. 2011

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Abstract-In healthy, mostly normotensive blacks, 19 salt-sensitive (SS) and 18 salt-resistant (SR), we tested the hypothesis that, in SS subjects, dietary NaCl loading induces its initial pressor effect by inducing a normal increase of cardiac output, while failing to induce a normal pressor-offsetting vasodilatation, consequent to its inhibition by asymmetrical dimethylarginine that is abnormally increased by NaCl. In SS and SR subjects, dietary NaCl loading, 250 from 30 mmol/d, over a 7-day period, induced similar, immediate increases in external Na ϩ balance (by day 2, Ϸ360 mmol), plasma volume (ϩ11%), and cardiac output (ϩ8%). In SR subjects, from day 1, transient decreases occurred in both systemic vascular resistance (nadir: Ϫ13%, day 2) and mean arterial pressure (nadir: Ϫ5%, day 2). In SS subjects, systemic vascular resistance did not change over days 1 to 3, whereas mean arterial pressure increased progressively after day 1, ultimately by 10 mm Hg. Failure of systemic vascular resistance to normally decrease, while cardiac output normally increased, accounted for salt's initial pressor effect in the SS subjects. In SS subjects, baseline plasma levels of asymmetrical dimethylarginine (0.76 mol/L) and symmetrical dimethylarginine (0.60 mol/L), which does not affect vasodilatation, approximated those in SR subjects. In SS but not SR subjects, NaCl loading induced increases in asymmetrical dimethylarginine on both days 2 (ϩ38%, median) and 7 (ϩ14%, median). Symmetrical dimethylarginine changed in neither group. For all of the subjects combined, changes in asymmetrical dimethylarginine on day 2 predicted changes in systemic vascular resistance (Rϭ0.751; PϽ0.001) and mean arterial pressure (Rϭ0.527; Pϭ0.006) on day 2 and similarly on day 7. These observations support the hypothesis tested. (Hypertension. 2011;58:380-385.) • Online Data Supplement Key Words: blood pressure Ⅲ blacks Ⅲ sodium chloride, dietary Ⅲ asymmetrical dimethylarginine Ⅲ symmetrical dimethylarginine B lood pressure (BP) that is, or is not, increased by dietary NaCl loading is deemed salt-sensitive (SS) or salt-resistant (SR), as are those so affected. Hypertension and fatal cardiovascular disease occur more frequently in the SS than in the SR. [1][2][3] In the traditionally formulated pathophysiological initiation of salt sensitivity, an abnormally enhanced renal reclamation of NaCl and commensurate water induces intravascular "volume loading" which leads to an excessive increase of cardiac output (CO) that alone initiates salt's pressor effect. 4,5 However, recent observations in SS blacks 6 suggest that the pressor effect of dietary NaCl loading might be initiated by NaCl's induction of a normal increase of CO, whose direct pressor effect fails to be offset by normal vasodilatation but instead is amplified by inhibition of this vasodilatation. Asymmetrical dimethylarginine (ADMA) is a major endogenous inhibitor of vasodilatation by inhibiting the endothelial synthesis of NO, which relaxes vascular smooth muscle. 7,8 In isolated rat arte...

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“…This observation concords with several studies in the literature showing the role of sodium homeostasis on the NO and the reninangiotensin pathways, as well as on arterial stiffness and PP. 21,32,33 In this study, the haemodynamic basis for the modulating role of genes on the age-PP relationship is important to analyse. It is important to note that all the mechanisms that contribute to alteration of large artery structure and function, particularly those occurring in central arteries, are known to be strongly influenced by age, and mostly to predominate in women.…”

Section: Papermentioning

confidence: 99%

Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study

Mourad

DuCailar

Rudnicki

et al. 2002

J Renin Angiotensin Aldosterone Syst

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Genes may modulate the changes of blood pressure (BP) with age; this possibility has never been studied for the age-related increase of pulse pressure (PP), although in older populations, PP is considered the stronger mechanical factor predicting cardiovascular mortality. In humans, the presence of the mutant allele C of the angiotensin II (Ang II) AT 1 -receptor or of the mutant allele T of the eNOS G 298 T gene polymorphisms is associated with enhanced contractile properties of conduit arteries in response to vasoconstrictive agents. In this study, we evaluated, in subjects with untreated essential hypertension, whether the presence of these mutant alleles or their combination might influence the age-related increase of PP. Three main findings emerged from the study and were particularly observed in women: 1) the presence of the C and/or of the T mutant alleles or their combination were associated with a steeper slope of the age versus PP curve, compared with subjects without the mutant allele; 2) the slope was more significantly enhanced when the two mutant alleles were associated in the same genotype; and 3) no comparable age-and gender-related changes in systolic, diastolic or mean BP were found according to this genetic classification. In subjects with essential hypertension, genes may modulate the age-mediated increase of PP. This finding gives new insights in the interactions between genes, mechanical factors and cardiovascular risk. IntroductionIncreased brachial pulse pressure (PP) is an independent predictor of CV risk, mainly for myocardial infarction.1 The value of PP is simultaneously influenced by an increase in systolic blood pressure (SBP) and a decrease of diastolic BP (DBP). In large populations over 50 years of age, cross-sectional and longitudinal studies have shown that cardiovascular (CV) mortality is not only positively correlated to the level of SBP, 2-4 but also that, at any given SBP value, CV mortality is higher when DBP is lower.4 PP is known to be influenced by three main haemodynamic mechanisms: the degree of ventricular ejection, the level of arterial stiffness and the pattern of wave reflections. 5 The two latter, but not ventricular ejection, have been shown to be significant and independent markers of CV risk.

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Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans

Cited by 49 publications

References 24 publications

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

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

Salt Sensitivity in Blacks

Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study

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