Salt Intake and Plasma Atrial Natriuretic Peptide and Nitric Oxide in Hypertension

Campese, Vito M.; Tawadrous, Medhat; Bigazzi, Roberto; Bianchi, Stefano; Mann, Adin; Oparil, Suzanne; Raij, Leopoldo

doi:10.1161/01.hyp.28.3.335

Cited by 93 publications

(72 citation statements)

References 63 publications

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“…Thus, our observations in humans indicate that unlike the rat, total NO production measured from 24-hour U NOX V does not increase with increased sodium intake, at least over a 3-day period. In accordance with the present findings, Campese et al 30 reported that plasma NO X concentrations did not increase in healthy subjects given a high-salt diet. Conversely, Facchini et al 31 reported an inverse relationship between change in BP and change in U NOX V in healthy subjects in response to low versus high sodium intakes.…”

Section: Discussionsupporting

confidence: 93%

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: Discussionsupporting

confidence: 93%

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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“…In the presence of hypertension and vasoconstriction, endogenous vasodilators such as members of the natriuretic family would be expected to be upregulated. Contrary to expectations, however, Blacks with hypertension induced by salt sensitivity have a reduction in one of the most potent of these vasodilators, A-type natriuretic peptide [36], compared to Whites with and without salt sensitivity and salt-resistant Blacks. This may represent a failure of microvascular protective measures against the effect of hypertension, resulting in the observed increase in minimal microvascular resistance.…”

Section: Discussioncontrasting

confidence: 70%

Differences in the association between type 2 diabetes and impaired microvascular function among Europeans and African Caribbeans

et al. 2005

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Aims/hypothesis: Diabetes is associated with microvascular damage in all populations, but diabetic patients of Black African descent (African Caribbeans) have a greater risk of vascular target organ damage than would be anticipated for any given blood pressure level. We investigated whether this may be due to differences in the microvasculature. Materials and methods: To assess the maximum hyperaemic response to heating and the post-ischaemic response, Laser Doppler fluximetry was performed on 51 and 100 Europeans, and on 66 and 88 African Caribbeans with and without diabetes, respectively. Subjects were aged between 40 and 65 years and recruited from the general population. Echocardiographic interventricular septal thickness (IVST) was measured as a proxy for vascular target organ damage. Results: In diabetic subjects of both ethnic groups, the maximum hyperaemic response and peak response to ischaemia were attenuated as compared to the corresponding non-diabetic subjects (p=0.08 for diabetic and 0.03 for non-diabetic Europeans; p=0.03 and 0.1 for African Caribbeans). Adjustment for cardiovascular risk factors, in particular insulin and blood pressure, abolished these differences in Europeans (p=0.8 for diabetic and 0.2 for non-diabetic Europeans), but not in African Caribbeans (p=0.03 and 0.05). Conclusions/interpretation: Persisting microvascular dysfunction in African Caribbeans may contribute to the increased risk of target organ damage observed in diabetes in this population. The weak contribution of conventional cardiovascular risk factors to these disturbances indicates that conventional therapeutic interventions may be less beneficial in these patients. There was a risk-factor-independent, inverse association between IVST and maximal hyperaemia. These ethnic differences in microvascular responses to temperature and arterial occlusion could account for increased target organ damage in African Caribbeans.

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“…4 In animal models of salt-sensitive hypertension, the increase in BP after salt loading is characterized by reduced NO production. 8,13,14 Similarly, in humans with salt-sensitive hypertension, salt loading was associated with decreased plasma and urinary levels of NO metabolites. 3,13,14 A variety of evidence suggests that reactive oxygen species contribute to impaired endothelial function in several forms of hypertension and that there is increased oxidative stress in the microvessels of spontaneously hypertensive rats and Dahl salt-sensitive hypertensive rats.…”

mentioning

confidence: 99%

“…8,13,14 Similarly, in humans with salt-sensitive hypertension, salt loading was associated with decreased plasma and urinary levels of NO metabolites. 3,13,14 A variety of evidence suggests that reactive oxygen species contribute to impaired endothelial function in several forms of hypertension and that there is increased oxidative stress in the microvessels of spontaneously hypertensive rats and Dahl salt-sensitive hypertensive rats. [15][16][17] A recent report by Lenda et al 7 has suggested that reactive oxygen species can also contribute to a reduced endothelium-dependent dilation in normotensive rats on a high-salt diet.…”

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confidence: 99%

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

et al. 2007

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Abstract-High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of L-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC 50 . Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium-independent vasorelaxants and may contribute to salt-sensitive hypertension. Key Words: acetylcholine Ⅲ hypertension Ⅲ oxidative stress Ⅲ salt sensitivity Ⅲ tempol E ndothelial cells modulate the reactivity of the underlying vascular smooth muscle cells by releasing endotheliumderived relaxing factors. 1,2 Previous studies have demonstrated that elevated dietary salt intake leads to an impaired relaxation of blood vessels to endothelium-dependent relaxations induced by a variety of vasodilator agents. 3-9 A possible contributor to impaired vascular relaxation to dilator stimuli in animals on a high-salt diet is an impaired function of the endothelium. 3-9 Impaired endothelium-dependent dilation in vessels of animals on a high-salt diet could occur either because the acetylcholine (Ach)-mediated production of NO by the endothelium is impaired or because of the failure of NO to cause vasodilation. [3][4][5][6][7][8][9] NO is a major regulator of vascular tone in humans. 10 Decreased production or bioavailability, or decreased vascular response to NO, has been implicated in the pathogenesis of human hypertension. 11,12 An increase in blood pressure (BP) in response to dietary sodium (salt sensitivity) is a well-documented phenomenon in humans and is considered to be an important factor in the pathogenesis of hypertension. 4 In animal models of salt-sensitive hypertens...

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Salt Intake and Plasma Atrial Natriuretic Peptide and Nitric Oxide in Hypertension

Cited by 93 publications

References 63 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

Differences in the association between type 2 diabetes and impaired microvascular function among Europeans and African Caribbeans

Mechanisms of Oxidative Stress-Induced Increase in Salt Sensitivity and Development of Hypertension in Sprague-Dawley Rats

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