Adaptation to increased dietary salt intake in the rat. Role of endogenous nitric oxide.

Shultz, Pamela J.; Tolins, Jonathan P.

doi:10.1172/jci116244

Cited by 242 publications

(169 citation statements)

References 44 publications

(59 reference statements)

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“…17 In rats, both acute and chronic administration of an NOS inhibitor causes renal vasoconstriction and a decrease in GFR as reported previously. 9,11,18,19 The present investigation also confirms that chronic L-NAME treatment induces decreases in total and regional blood flow to the kidney, as well as GFR, as compared with the values obtained from nontreated control animals. As observed with chronic tempol treatment in our earlier study, 6 acute intrarenal infusion of tempol in L-NAME-hypertensive rats in the present study also increased GFR.…”

Section: Discussionsupporting

confidence: 86%

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

Kopkan

Majid

2006

Hypertension

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Abstract-An enhancement of superoxide (O 2 Ϫ ) activity was shown to contribute to the development of hypertension induced by NO deficiency. To better understand the mechanistic role of O 2 Ϫ in this NO-deficient hypertension, we evaluated the renal responses to acute intraarterial administration of an O 2 Ϫ scavenger, tempol (50 g/min per 100 g of body weight) in anesthetized male Sprague-Dawley rats treated with NO synthase inhibitor nitro-L-arginine methyl ester (15 mg/kg per day in drinking water, nϭ7) for 4 weeks, which caused increases in mean arterial pressure (146Ϯ3 versus 124Ϯ2 mm Hg) compared with normotensive control rats (nϭ6). Hypertensive rats had higher renal vascular resistance (29Ϯ2 versus 20Ϯ1 mm Hg/mL per minute per gram), as well as lower renal blood flow (5.2Ϯ0.3 versus 6.3Ϯ0.2 mL/min per gram; cortical blood flow, 153Ϯ13 versus 191Ϯ8 perfusion units; medullary blood flow, 43Ϯ2 versus 51Ϯ3 perfusion units) and glomerular filtration rate (0.69Ϯ0.04 versus 0.90Ϯ0.05 mL/min per gram) without a significant difference in urinary sodium excretion (0.81Ϯ0.07 versus 0.86Ϯ0.12 mol/min per gram) compared with normotensive rats. Urinary 8-isoprostane excretion rate (6.8Ϯ0.7 versus 4.5Ϯ0.3 pg/min per gram) was higher in hypertensive than normotensive rats. Intraarterial infusion of tempol did not alter renal function in normotensive rats. However, tempol significantly decreased renal vascular resistance by 12Ϯ2% and urinary 8-isoprostane excretion rate by 24Ϯ4% and increased renal blood flow by 10Ϯ2%, cortical blood flow by 9Ϯ2%, medullary blood flow by 15Ϯ6%, glomerular filtration rate by 11Ϯ3%, and urinary sodium excretion by 19Ϯ5% in hypertensive rats. These data indicate that enhanced O 2 Ϫ activity modulates renal hemodynamics and excretory function during reduced NO production and, thus, contributes to the pathophysiology of the NO-deficient form of hypertension. A n imbalance between the production and the degradation of reactive oxygen species such as superoxide anion (O 2 Ϫ ) leads to the condition termed as "oxidative stress." It has been suggested that oxidative stress is involved in the pathophysiology of many forms of hypertension. 1-3 Treatment with an O 2 Ϫ scavenging agent, tempol (4-hydroxytetramethylpiperidime-1-oxyl), significantly reduces blood pressure in different hypertensive models 4,5 indicating that O 2 Ϫ plays a role in the development of hypertension. Recently, we also demonstrated that chronic treatment with tempol attenuated the development of hypertension and salt sensitivity in rats induced by chronic inhibition of NO synthase (NOS) in rats. 6 These results indicate that an enhanced O 2 Ϫ generation is involved in the pathogenesis of an NO-deficient form of hypertension. However, the exact mechanistic role of O 2 Ϫ in mediating the salt sensitivity and hypertension in the condition of NO deficiency has not yet been clearly defined.NO acts as an endogenous antioxidative agent by reacting with O 2 Ϫ generated in the living tissues, thus it provides a protective function aga...

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Section: Discussionsupporting

confidence: 86%

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

Kopkan

Majid

2006

Hypertension

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“…For example, in the normal rat, dietary sodium loading evokes a large increase in total NO production, detectable as increased U NOX V. 10,11,23,24 There is evidence that dietary sodium loading upregulates the neuronal NOS protein in the inner medullary collecting duct, 24 as well as increasing glomerular endothelial nitric oxide synthase (eNOS) messenger RNA and NO production 25 after 3 to 4 days of high salt intake. Functional studies indicate that total renal blood flow and blood flow to the papilla are under enhanced NO-dependent vasodilatory tone when salt intake is high.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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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“…When steps are taken to prevent increases in renal perfusion pressure, NO synthesis inhibition causes a clear fall in sodium excretion. 19 Several studies have demonstrated that the renal pressure-natriuresis mechanism is greatly impaired after administration of NO synthesis inhibitors. 20 -21 To evaluate the potential role of the renal sympathetic nerves in L-NAME-induced hypertension, we investigated the influence of renal denervation on the hypertension induced by long-term oral administration of L-NAME.…”

Section: Discussionmentioning

confidence: 99%

Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent.

et al. 1994

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Recent studies have indicated that chronic administration of iV"-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elevated after L-NAME administration. To evaluate the potential role of the renal sympathetic nerves in L-NAMEinduced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawley rats (n=8 each): (1) sham-operated vehicle-treated, (2) shamoperated L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L-NAME-treated. After renal denervation or sham surgery, L-NAME was added to the drinking N itric oxide (NO) is now known to be an important participant in a variety of physiological processes, including several that influence arterial pressure.1 Acute administration of substituted arginine analogues that inhibit NO synthesis, including /V°'-nitro-Larginine methyl ester (L-NAME), results in a prompt increase in arterial pressure.2 -3 The immediate increase in arterial pressure may be principally due to an increased vascular smooth muscle tone as a consequence of decreased endothelial synthesis of NO. Increases in sympathetic nerve activity have been described after acute NO synthesis inhibition, 46 suggesting that neurogenic mechanisms may also contribute to the acute increase in arterial pressure.Several laboratories have recently reported that continued administration of inhibitors of NO synthesis induces a sustained hypertension.79 Although a precise mechanism by which continued NO synthesis inhibition may induce chronic hypertension remains to be identified, renal control of fluid and electrolyte balance is thought to play a dominant role in the long-term control of arterial pressure in both normal and pathophysiological states.10 ' 11 Renal sympathetic nerve activity is known to be increased at least acutely after administration of NO synthesis inhibitor, 46 and activation of the renal sympathetic nerves is known to inhibit renal sodium excretion and promote renal renin secretion. 12 Thus, we hypothesized that chronic L-NAME-induced hypertension may be, in part, the result of a sustained activation of the renal sympathetic nerves and the resultant resetting of renal fluid and electrolyte balance water (70 rngVlOO mL) for 4 weeks, and arterial pressure was measured weekly by the tail-cuff method. L-NAME treatment caused a progressive increase in arterial pressure in shamoperated rats, rising to 154±6 mm Hg by week 4 of treatment compared with 115±2 mm Hg in the vehicle-treated shamoperated group (P<.005). In contrast, the development of hypertension was significantly delayed and attenuated in renaldenervated rats treated with L-NAME. The results of our study suggest that L-NAME-induced hypertension may be partly mediated by or is at least dependent on the integrity of the renal nerves. Key Words • blood pressure • end...

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Adaptation to increased dietary salt intake in the rat. Role of endogenous nitric oxide.

Cited by 242 publications

References 44 publications

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats

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

Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent.

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