Abstract
Oxidative stress in blood vessels and the kidney in hypertension can be induced by diverse vasoconstrictor mechanisms, including blockade of nitric oxide synthase and activation of angiotensin II type I receptors and thromboxane receptors. It can cause vasoconstriction via bioinactivation of nitric oxide, and by nitric oxide synthase independent mechanisms that include increased generation of endothelin-1 and the effects of superoxide anion and hydrogen peroxide on vascular smooth muscle cells. Oxidative stress can accompany hypertension in many models including the spontaneously hypertensive rat, the angiotensin II-infused rat, renovascular hypertension, the deoxycorticosterone acetate-salt model, and obesity-related hypertension. In the kidney, NADPH oxidase-generating superoxide anion is expressed in the vasculature, interstitium, juxtaglomerular apparatus, and the distal nephron. Much progress has been made in defining the pathways that intervene between agonist stimulation of blood vessels and reactive oxygen species-mediated contractile and renal functional responses in animal models in hypertension.
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References and Recommended Reading
Vanhouette PM: Endothelium-derived free radicals: for worse and for better. J Clin Invest 2001, 107:23–25.
Cosentino F, Patton S, d’Uscio LV, et al.: Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest 1998, 101:1530–1537.
Klein T, Neuhaus K, Reutter F, et al.: Generation of 8-epi prostaglandin F(2a) in isolated rat kidney glomeruli by radical-independent mechanism. Br J Pharmacol 2001, 133:643–650. This study challenges the hypothesis that isoprostanes are quantitative markers of oxidative stress, at least in isolated glomeruli.
Schnackenberg CG, Welch WJ, Wilcox CS: TP receptormediated vasoconstriction in microperfused afferent arterioles: role O2- and NO. Am J Physiol 2000, 48:F302-F308. This study shows potent counter-regulation of afferent arterial contraction by TP receptor-dependent generation of NO and O2.
Schnackenberg CG, Welch WJ, Wilcox CS: Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension 1998, 32:59–64.
Usui M, Egashira K, Kitamoto S, et al.: Pathogenic role of oxidative stress on vascular angiotensin-converting enzyme activation in long-term blockade of nitric oxide synthesis in rats. Hypertension 1999, 34:546–551.
Kitamoto S, Egashira K, Kataoka C, et al.: Chronic inhibition of nitric oxide synthesis in rats increases aortic superoxide anion production via the action of angiotensin II. J Hypertension 2000, 18:1795–1800. This study provides new evidence that oxidative stress contributes to the prolonged effects of NOS inhibition.
Kahler J, Ewert A, Weckmuller J, et al.: Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth muscle cells. J Cardiovasc Pharmacol 2001, 38:49–57.
Nagase M, Ando K, Nagase T, et al.: Redox-sensitive regulation of lox-1 gene expression in vascular endothelium. Biochem Biophys Res Commun 2001, 281:720–725.
Vaziri ND, Wang XQ, Oveisi F, et al.: Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension 2000, 36:142–146. This study describes an important new model of oxidative stress and hypertension.
Ding Y, Gonick HC, Vaziri ND: Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells. Am J Hypertens 2000, 13:552–555.
Lambeth JD, Cheng G, Arnold RS, et al.: Novel homologs of gp91phox. TIBS 2000, 25:459–461.
Gorlach A, Brandes RP, Nguyen K, et al.: A gp 91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res 2000, 87:26–32.
Lassègue B, Sorescu D, Yin Q, et al.: Novel gp 91phox homologues in vascular smooth muscle cells nox1 mediates angiotensin II-induced superoxide formation and redoxsensitive signaling pathways. Circ Res 2001, 88:888–894.
Geiszt M, Kopp JB, Várnai P, et al.: Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci U S A 2000, 97:8010–8014.
Chabrashvili T, Tojo A, Onozato M, et al.: Expression and cellular localization of classic NADPH oxidase subunites in the SHR kidney. Hypertension 2001, In Press.
Majid DSA, Taher KA, Nishiyama A: Administration of a superoxide scavenger, tempol, causes diuresis and natiuresis in anesthetized dogs treated with nitro-L-arginine. J Am Soc Nephrol 2000, 11:337A.
Meyer TN, Schwesinger C, Ye J, et al.: Reassembly of the tight junction after oxidative stress depends on tyrosine kinase activity. J Biol Chem 2001, 276:22048–22055.
Hahn S, Kuemmerle N, Chan W, et al.: Glomerulosclerosis in the remnant kidney rat is modulated by dietary a-tocopherol. J Am Soc Nephrol 1998, 9:2089–2095.
Chan W, Krieg RJJ, Norkus EP, et al.: Alpha-tocopherol reduces proteinuria, oxidative stress, and expression of transforming growth factor beta 1 in IgA nephropathy in the rat. Mol Genet Metab 1998, 63:224–229.
Chatterjee PK, Cuzzocrea S, Brown PA, et al.: Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int 2000, 58:658–673.
Wilcox CS, Welch WJ: Interaction between nitric oxide and oxygen radicals in regulation of tubuloglomerular feedback. Acta Physiol Scand 2000, 168:119–124.
Sun D, Samuelson LC, Yang T, et al.: Mediation of tubuloglomerular feedback by adenosine: Evidence from mice lacking adenosin 1 receptors. Proc Natl Acad Sci U S A 2001, 98:9983–9988.
Wilcox CS, Welch WJ: Macula densa nitric oxide synthase: Expression, regulation, and function. Kidney Int 1998, 54:S53-S57.
Wilcox CS, Welch WJ, Murad F, et al.: Nitric oxide synthase in macula densa regulates glomerular capillary pressure. Proc Natl Acad Sci 1992, 89:11993–11997.
Welch WJ, Tojo A, Wilcox CS: Roles of NO and oxygen radicals in tubuloglomerular feedback in SHR. Am J Physiol 2000, 278:F769-F776.
McIntyre M, Bohr DF, Dominiczak AF: Endothelial function in hypertension. Hypertension 1999, 34:539–545.
McIntyre M, Hamilton CA, Rees DD, et al.: Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension. Hypertension 1997, 30:1517–1524.
Kerr S, Brosnan MJ, McIntyre M, et al.: Superoxide anion production is increased in a model of genetic hypertension: role of endothelium. Hypertension 1999, 33:1353–1358.
Welch WJ, Wilcox CS: AT1 receptor antagonist combats oxidative stress and restores nitric oxide signaling in the SHR. Kidney Int 2001, 59:1257–1263. This study describes the role of AT1 receptors in oxidative stress-dependent regulation of TGF.
Ichihara A, Hayashi M, Hirota N, et al.: Superoxide inhibits neuronal nitric oxide synthase influeces on afferent arterioles in spontaneously hypertensive rats. Hypertension 2001, 37:630–634.
Schnackenberg C, Wilcox CS: Two-week administration of tempol attenuates both hypertension and renal excretion of 8-iso prostaglandin F2α. Hypertension 1999, 33:424–428.
Chen X, Touyz RM, Park JB, et al.: Antioxidant effects of vitamin C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. Hypertension 2001, 38:606–611.
Pukui T, Ishizaka N, Rajagopalan S, et al.: Griendling. P22phox mRNA expression and NADPH oxidase activity are increased in aortas form hypertensive rats. Circ Res 1997, 80:45–51.
Haugen EN, Croatt AJ, Nath KA: Angiotensin II induses renal oxidant stress in vivo and heme oxygenase-1 in vivo and in vitro. Kidney Int 2000, 58:144–152.
Reckelhoff JF, Zhang H, Srivastava K, et al.: Subpressor doses of angiotensin II increase plasma F2-isoprostanes in rats. Hypertension 2000, 35:476–479.
Tojo A, Kimoto N, Wilcox CS: Renal expression of constitutive NOS and DDAH: separate effects of salt intake and angiotensin. Kidney Int 2000, 58:2075–2083.
Mervaala EM, Cheng JZ, Tikkanen I, et al.: Endothelial dysfunction and xanthine oxidoreductase activity in rats with human renin and angiotensinogen genes. Hypertension 2001, 37:414–418. This study suggests that xanthine oxidoreductase is important in oxidative stress in Ang II-dependent hypertension.
Nishiyama A, Fukui T, Fujisawa Y, et al.: Systemic and regional hemodynamic responses to tempol in angiotensin II-infused hypertensive rats. Hypertension 2001, 37:77–83. 40. Ortiz MC, Manriquez MC, Romero JC, et al.: Antioxidants blood angiotensin II-induced increases in blood pressure and endothelin. Hypertension 2001, 38:655-659.
Barton CH, Ni Z, Vaziri ND: Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension. Kidney Int 2001, 60:1083–1087.
Lerman LO, Nath KA, Rodriguez-Porcel M, et al.: Increased oxidative stress in experimental renovascular hypertension. Hypertension 2001, 37:541–546.
Dobrian AD, Schriver SD, Prewitt RL: Role of angiotensin II and free radicals in blood pressure regulation in a rat model of renal hypertension. Hypertension 2001, 38:361–366.
Touyz RM, Schiffrin EL: Ang II-stimulated superoxide production is mediated via phospholipase D in human vascular smooth muscle cells. Hypertension 1999, 34:976–982.
Lassegue B, Ushio-Fukai M, Griendling KK: Novel aspects of angiotensin II signalling in vascular smooth muscle. Presented at 5th Internet World Congress for Biomedical Science (INABIS). Hamilton, Ontario. December 7-16, 1998.
Galle J, Stunz P, Schollmeyer P, et al.: Oxidized LDL and lipoprotein (a) stimulate renin release from juxtaglomerular cells. Kidney Int 1995, 47:45–52.
Ichiki T, Takeda K, Tokunou T, et al.: Reactive oxygen speciesmediated homologous downregulation of angiotensin II type 1 receptor mRNA by angiotensin II. Hypertension 2001, 37:535–540.
Nickenig G, Strehlow K, Bäumer AT, et al.: Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression. Br J Pharm 2000, 131:795–803.
Somers Y, Mavromatis K, Galis ZS, et al.: Vascular superoxide production and vasomotor function in hypertension induced by deoxycortisone acetate-salt. Circulation 2000, 101:1722–1728.
Wu R, Millette E, Wu L, et al.: Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats. J Hypertens 2001, 19:741–748.
Nicod L, Rodriguez S, Letang JM, et al.: Antioxidant status, lipid peroxidation, mixed function oxidase and UDPglucuronyl transferase activities in livers from control and DOCA-salt hypertensive male Sprague Dawley rats. Mol Cell Biochem 2000, 203:33–39.
Beswick RA, Zhang H, Marable D, et al.: Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension 2001, 37:781–786. The study describes the role of oxidative stress in hypertension and renal damage in a low renin model.
Roberts CK, Vaziri ND, Wang XQ, et al.: Enhanced NO inactivation and hypertension induced by a high-fat, refinedcarbohydrate diet. Hypertens 2000, 36:423–429.
Poirier B, Lannaud-Bournoville M, Conti M, et al.: Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats. Nephrol Dial Transplant 2000, 15:467–476.
Dobrian AD, Davies MJ, Schriver SD, et al.: Oxidative stress in a rat model of obesity-induced hypertension. Hypertens 2001, 37:554–560. This study describes the role of oxidative stress in a prolonged model of obesity-related hypertension.
Stulak JM, Lerman A, Porcel MR, et al.: Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation. J Am Soc Nephrol 2001, 12:1882–1891.
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Wilcox, C.S. Reactive oxygen species: Roles in blood pressure and kidney function. Current Science Inc 4, 160–166 (2002). https://doi.org/10.1007/s11906-002-0041-2
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DOI: https://doi.org/10.1007/s11906-002-0041-2