Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation

Hezel, Michael; Peleli, Maria; Liu, Ming; Zollbrecht, Christa; Jensen, Boye L.; Checa, Antonio; Giulietti, Alessia; Wheelock, Craig E.; Lundberg, Jon O.; Weitzberg, Eddie; Carlström, Mattias

doi:10.1016/j.freeradbiomed.2016.07.025

Cited by 66 publications

(69 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 88%

“…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. Our experiments on the effects of l ‐NAME treatment on the control of renal vascular tone did not reveal a differential contribution of NO to renal vascular tone regulation with the exception of RMF, which accounts only for a small fraction of total RBF15 and therefore makes only a small contribution to RVR.…”

Section: Discussionmentioning

confidence: 88%

“…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%

See 3 more Smart Citations

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…Theoretically, reductions of NO 3 − and NO 2 − to NO could restore NO homeostasis, maintain the steady-state NO levels, and are considered as stable storage pools for NO-like bioactivity [22]. So, considering the role of NO as the key regulator of vascular homeostasis and natural vasodilator, supplementation with inorganic NO 3 − and NO 2 − have been investigated as potential therapeutic options in cardiovascular disease, including HTN, and in states renal dysfunction [23,24,25,26]. Currently, a large body of evidence supports a crucial role of NO 3 − and NO 2 − in the regulation and modulation of blood flow, endothelial function, and blood pressure [26,27,28].…”

Section: Introductionmentioning

confidence: 99%

Association between Dietary Intakes of Nitrate and Nitrite and the Risk of Hypertension and Chronic Kidney Disease: Tehran Lipid and Glucose Study

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background and Aim: The association of habitual intakes of dietary nitrate (NO3−) and nitrite (NO2−) with blood pressure and renal function is not clear. Here, we investigated a potential effect of dietary NO3− and NO2− on the occurrence of hypertension (HTN) and chronic kidney disease (CKD). Methods: A total of 2799 Iranian adults aged ≥20 years, participating in the Tehran Lipid and Glucose Study (TLGS), were included and followed for a median of 5.8 years. Dietary intakes of NO3− and NO2− were estimated using a semi-quantitative food frequency questionnaire. Demographics, anthropometrics, blood pressure and biochemical variables were evaluated at baseline and during follow-up examinations. To identify the odds ratio (OR) and 95% confidence interval (CI) of HTN and CKD across tertile categories of residual energy-adjusted NO3− and NO2− intakes, multivariate logistic regression models were used. Results: Dietary intake of NO3− had no significant association with the risk of HTN or CKD. Compared to the lowest tertile category (median intake < 6.04 mg/day), the highest intake (median intake ≥ 12.7 mg/day) of dietary NO2− was accompanied with a significant reduced risk of HTN, in the fully adjusted model (OR = 0.58, 95% CI = 0.33–0.98; p for trend = 0.054). The highest compared to the lowest tertile of dietary NO2− was also accompanied with a reduced risk of CKD (OR = 0.50, 95% CI = 0.24–0.89, p for trend = 0.07). Conclusion: Our findings indicated that higher intakes of NO2− might be an independent dietary protective factor against the development of HTN and CKD, which are major risk factors for adverse cardiovascular events.

show abstract

A 25-Year Long Journey into the World of NO

Mazzanti

Vignini

Emanuelli

2020

The First Outstanding 50 Years of “Università Politecnica Delle Marche”

View full text Add to dashboard Cite

Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation

Cited by 66 publications

References 50 publications

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Association between Dietary Intakes of Nitrate and Nitrite and the Risk of Hypertension and Chronic Kidney Disease: Tehran Lipid and Glucose Study

A 25-Year Long Journey into the World of NO

Contact Info

Product

Resources

About