Relationship Between Endothelin and Nitric Oxide Pathways in the Onset and Maintenance of Hypertension in Children and Adolescents

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2021 Jun 4

PMID 34085102

Citations 9

Authors

Simonetta Genovesi

Marco Giussani

Antonina Orlando

Giulia Lieti

Francesca Viazzi

Gianfranco Parati

Affiliations

Soon will be listed here.

Abstract

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

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References

Davenport A, Hyndman K, Dhaun N, Southan C, Kohan D, Pollock J . Endothelin. Pharmacol Rev. 2016; 68(2):357-418. PMC: 4815360. DOI: 10.1124/pr.115.011833. View

Kedzierski R, Yanagisawa M . Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001; 41:851-76. DOI: 10.1146/annurev.pharmtox.41.1.851. View

Hemmens B, Mayer B . Enzymology of nitric oxide synthases. Methods Mol Biol. 2000; 100:1-32. DOI: 10.1385/1-59259-749-1:1. View

Robbins R, Grisham M . Nitric oxide. Int J Biochem Cell Biol. 1997; 29(6):857-60. DOI: 10.1016/s1357-2725(96)00167-7. View

Selvaraju V, Ayine P, Fadamiro M, Babu J, Brown M, Geetha T . Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction. Oxid Med Cell Longev. 2019; 2019:9604740. PMC: 6817929. DOI: 10.1155/2019/9604740. View

Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S . Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005; 23(1):7-17. DOI: 10.1097/00004872-200501000-00004. View

Spinella F, Caprara V, Cianfrocca R, Rosano L, Di Castro V, Garrafa E . The interplay between hypoxia, endothelial and melanoma cells regulates vascularization and cell motility through endothelin-1 and vascular endothelial growth factor. Carcinogenesis. 2014; 35(4):840-8. PMC: 3988429. DOI: 10.1093/carcin/bgu018. View

Correia-Costa L, Sousa T, Morato M, Cosme D, Afonso J, Areias J . Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function. Br J Nutr. 2016; 116(5):805-15. DOI: 10.1017/S0007114516002804. View

Barton M . Aging and endothelin: determinants of disease. Life Sci. 2014; 118(2):97-109. DOI: 10.1016/j.lfs.2014.09.009. View

10.

Wang Y, Chen S, Du J . Bosentan for Treatment of Pediatric Idiopathic Pulmonary Arterial Hypertension: State-of-the-Art. Front Pediatr. 2019; 7:302. PMC: 6663967. DOI: 10.3389/fped.2019.00302. View

11.

Takasuka T, Sakurai T, Goto K, Furuichi Y, Watanabe T . Human endothelin receptor ETB. Amino acid sequence requirements for super stable complex formation with its ligand. J Biol Chem. 1994; 269(10):7509-13. View

12.

Schweizer A, Valdenaire O, Nelbock P, Deuschle U, Dumas Milne Edwards J, Stumpf J . Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. Biochem J. 1998; 328 ( Pt 3):871-7. PMC: 1218999. DOI: 10.1042/bj3280871. View

13.

Zhou L, Zhu D . Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide. 2009; 20(4):223-30. DOI: 10.1016/j.niox.2009.03.001. View

14.

Katona E, Settakis G, Varga Z, Paragh G, Bereczki D, Fulesdi B . Target-organ damage in adolescent hypertension. Analysis of potential influencing factors, especially nitric oxide and endothelin-1. J Neurol Sci. 2006; 247(2):138-43. DOI: 10.1016/j.jns.2006.04.007. View

15.

Yuan W, Cheng G, Li B, Li Y, Lu S, Liu D . Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis. Blood Press. 2016; 26(3):139-149. DOI: 10.1080/08037051.2016.1208730. View

16.

Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K . Global Prevalence of Hypertension in Children: A Systematic Review and Meta-analysis. JAMA Pediatr. 2019; 173(12):1154-1163. PMC: 6784751. DOI: 10.1001/jamapediatrics.2019.3310. View

17.

Masaki T . Historical review: Endothelin. Trends Pharmacol Sci. 2004; 25(4):219-24. DOI: 10.1016/j.tips.2004.02.008. View

18.

Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R . Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature. 1994; 368(6473):703-10. DOI: 10.1038/368703a0. View

19.

Hermann M, Flammer A, Luscher T . Nitric oxide in hypertension. J Clin Hypertens (Greenwich). 2006; 8(12 Suppl 4):17-29. PMC: 8109558. DOI: 10.1111/j.1524-6175.2006.06032.x. View

20.

Orlando A, Viazzi F, Giussani M, Nava E, Cazzaniga E, Bonino B . Endothelin-1/nitric oxide balance and HOMA index in children with excess weight and hypertension: a pathophysiological model of hypertension. Hypertens Res. 2019; 42(8):1192-1199. DOI: 10.1038/s41440-019-0253-3. View