Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension

Carlström, Mattias; Persson, A. Erik G.; Larsson, Erik; Hezel, Michael; Scheffer, P; Teerlink, Tom; Weitzberg, Eddie; Lundberg, Jon O.

doi:10.1093/cvr/cvq366

Cited by 223 publications

(195 citation statements)

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“…Therefore, we tested whether oral nitrate supplementation lowers arterial pressure in sunitinib‐treated rats. We found that nitrate administered at a dose that effectively lowers arterial pressure in rats with states of low NO availability such as sodium chloride‐induced hypertension,21 senescence,22 diabetes mellitus,31 and in spontaneously hypertensive rats32 did not mitigate sunitinib‐induced hypertension. Furthermore, nitrate supplementation did not affect arterial pressure in controls, which is in agreement with findings by others showing that nitrate administration to healthy 3‐month‐old rats is without significant effects on arterial pressure 22.…”

Section: Discussionmentioning

confidence: 89%

“…Renal NO X excretion is less in sunitinib‐treated rats than in controls,11, 16 which is indicative of reduced NO formation and availability 29. Oral nitrate supplementation has been shown to lower arterial pressure in humans30 and in rats 21, 22. Therefore, we tested whether oral nitrate supplementation lowers arterial pressure in sunitinib‐treated rats.…”

Section: Discussionmentioning

confidence: 99%

“…Endogenous NO is formed by conversion of l ‐arginine to citrulline and NO by 3 NO synthases (NOS1‐3) 18. In addition, NO can be formed in mammals independent of NOS activity by sequential reduction of nitrate via nitrite to NO, and oral nitrate supplementation has been shown to reduce arterial pressure as well as renal damage 19, 20, 21, 22, 23…”

Section: Introductionmentioning

confidence: 99%

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Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

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BackgroundThe tyrosine kinase inhibitor sunitinib causes hypertension associated with reduced nitric oxide (NO) availability, elevated renal vascular resistance, and decreased fractional sodium excretion. We tested whether (1) nitrate supplementation mitigates sunitinib‐induced hypertension and NO contributes less to renal vascular resistance as well as fractional sodium excretion regulation in sunitinib‐treated rats than in controls; and (2) renal soluble guanylate cyclase (sGC) is downregulated and sGC activation lowers arterial pressure in rats with sunitinib‐induced hypertension.Methods and ResultsArterial pressure responses to nitrate supplementation and the effects of systemic and intrarenal NO synthase (NOS) inhibition on renal hemodynamics and fractional sodium excretion were assessed in sunitinib‐treated rats and controls. Renal NOS and sGC mRNA as well as protein abundances were determined by quantitative polymerase chain reaction and Western blot. The effect of the sGC activator cinaciguat on arterial pressure was investigated in sunitinib‐treated rats. Nitrate supplementation did not mitigate sunitinib‐induced hypertension. Endothelium‐dependent reductions in renal vascular resistance were similar in control and sunitinib‐treated animals without and with systemic NOS inhibition. Selective intrarenal NOS inhibition lowered renal medullary blood flow in control but not in sunitinib‐treated rats without significant effects on fractional sodium excretion. Renal cortical sGC mRNA and sGC α1‐subunit protein abundance were less in sunitinib‐treated rats than in controls, and cinaciguat effectively lowered arterial pressure by 15‐20 mm Hg in sunitinib‐treated rats.ConclusionsRenal cortical sGC is downregulated in the presence of intact endothelium‐dependent renal vascular resistance regulation in developing sunitinib‐induced hypertension. This suggests that sGC downregulation occurs outside the renal vasculature, increases renal sodium retention, and contributes to nitrate resistance of sunitinib‐induced hypertension.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

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“…Levels of endogenous NO decline with aging or due to metabolic dysfunctions and nitrite and nitrate derived from food sources or when administered in a clinical setting for specific diseases have been shown to restore NO homeostasis (Bryan et al, 2007;Carlström et al, 2010;Celermajer et al, 1994;Davignon & Ganz, 2004;Egashira et al, 1993;Gerhard, Roddy, Creager, & Creager, 1996;Lundberg, Weitzberg, & Gladwin, 2008;Taddei, Virdis, Ghiadoni, Sudano, & Salvetti, 2001). Dietary nitrite and nitrate have been shown to protect against ischemic heart injury, prevent vascular inflammation and improve exercise performance and could, within limits, be considered indispensable nutrients (Bryan et al, 2007;Carlström et al, 2011;Kleinbongard et al, 2006;Rassaf et al, 2007). While there are upper limits to nitrite and nitrate consumption, there is a high endogenous production of nitrite (5.18 mg nitrite per day, one hot dog of 50 g would provide 0.026 mg nitrite and 4.88 mg nitrate; Milkowski, 2011).…”

Section: N-nitroso Compoundsmentioning

confidence: 99%

0908 The role of red and processed meat in colorectal cancer development: A perspective

Smet¹

2016

Journal of Animal Science

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This paper is based on a workshop held in Oslo, Norway in November 2013, in which experts discussed how to reach consensus on the healthiness of red and processed meat. Recent nutritional recommendations include reducing intake of red and processed meat to reduce cancer risk, in particular colorectal cancer (CRC). Epidemiological and mechanistic data on associations between red and processed meat intake and CRC are inconsistent and underlying mechanisms are unclear. There is a need for further studies on differences between white and red meat, between processed and whole red meat and between different types of processed meats, as potential health risks may not be the same for all products. Better biomarkers of meat intake and of cancer occurrence and updated food composition databases are required for future studies. Modifying meat composition via animal feeding and breeding, improving meat processing by alternative methods such as adding phytochemicals and improving our diets in general are strategies that need to be followed up.

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“…69,70) In animal model of unilateral nephrectomy and high-salt diet hypertension, dietary nitrate attenuated hypertension by restoring bioactive nitrogen oxides in the tissues and reducing oxidative stress markers like ADMA in plasma and urine. 71) Not only L-arginine, but also nitrate is possible to be a candidate as a tool of dietary supplementation to produce NO for treatment for hypertension. Ingestion of dietary nitrate is reported to elevate plasma nitrite and cyclic guanosine monophosphate, a sensitive indicator of NO bioactivity.…”

Section: Experimental Evidence Of the Association Between Endothelialmentioning

confidence: 99%

Blood Pressure Variability and Vascular Dysfunction in Essential Hypertension

Okumura

Cheng

2012

J Korean Soc Hypertens

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❙ABSTRACT❙There are several aspects of blood pressure. Clinically, how to best assess blood pressure average and variability is still a matter of the ongoing debate. Besides office blood pressure, we must pay more careful attention focused on hypertension with blood pressure fluctuation. Impaired endothelial function is intimately associated with the development of hypertension and atherosclerosis. In this review, we describe the relation between endothelial dysfunction and hypertension, the effect of gene polymorphism on endothelial dysfunction, the effects of antihypertensive agents and dietary supplementation on impaired endothelial function in hypertension. In order to predict the future atherosclerosis and cardiovascular events in subjects with hypertension, the adequate assessment of endothelial function is one of the most reliable markers.Furthermore, we discuss the close relationship between blood pressure variability and endothelial function. Blood pressure variability during a day or a week is an important, new risk factor for cardiovascular disease and restoring impaired endothelial function might be a target to prevent blood pressure variation and future cardiovascular events.

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Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension

Abstract: Dietary inorganic nitrate is strongly protective in this model of renal and cardiovascular disease. Future studies will reveal if nitrate contributes to the well-known cardioprotective effects of a diet rich in vegetables.

Cited by 223 publications

References 54 publications

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

0908 The role of red and processed meat in colorectal cancer development: A perspective

Blood Pressure Variability and Vascular Dysfunction in Essential Hypertension

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