Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats

Kopkan, Libor; Castillo, Alexander; Navar, L. Gabriel; Majid, Dewan S. A.

doi:10.1152/ajprenal.00090.2005

Cited by 64 publications

(81 citation statements)

References 41 publications

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“…To our knowledge, no previous study addressed this specific issue of determining the role of O 2 Ϫ in modulating renal function in L-NAME-induced hypertensive rats. As we reported previously, 12 intraarterial administration of tempol provides a more direct assessment of the responses to O 2 Ϫ scavenging on renal hemodynamics and excretory function without appreciable changes in blood pressure that are usually associated with systemic administration of tempol. 13,14 …”

mentioning

confidence: 77%

“…12 The right jugular vein was catheterized for intravenous administration of solutions. The cannula introduced into the right femoral artery was connected with the AcqKnowledge data acquisition system Biopac to allow continuous monitoring of arterial blood pressure.…”

Section: Methodsmentioning

confidence: 99%

“…A polyethylene tube PE-10 (OD, 0.61 mm) catheter, which was tapered Ϸ40% to 50%, was inserted Ϸ2 to 3 mm deep into the renal artery from the aorta via the left femoral artery to allow intraarterial administration of drugs directly into the kidney at a rate of 5 L/min. 12 This procedure of inserting the tapered catheter usually does not compromise the renal blood flow (RBF) measurements, because it was observed in pilot experiments that there was no significant alteration of baseline RBF before and after the catheter insertion.…”

Section: Methodsmentioning

confidence: 99%

“…Tempol (Sigma) was infused at a dose of 50 g/min per 100 g of body weight. This dose of tempol was selected based on findings in our earlier acute studies in rats 12 and dogs 7,16 that showed significant reductions in the urinary 8-isoprostane excretion rate (U ISO V; marker for endogenous O 2 Ϫ activity). At the midpoint of the clearance collection period, an arterial blood sample was collected from the femoral arterial cannula to measure plasma inulin and sodium concentration.…”

Section: Methodsmentioning

confidence: 99%

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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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mentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Kopkan

Majid

2006

Hypertension

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“…These improvements may be related to improved endothelial function since the hypertensive effect of salt loading appears linked to oxidative stress and reduced NO bioavailability, which can be exacerbated by NO inhibition 1,[165][166][167] . In patients with mild hypertension those with lower self-reported daily sodium intake had significantly higher brachial artery flow-mediated dilatation, suggesting improved endothelial function in patients with lower sodium intake 1,168 .…”

Section: Salt Intakementioning

confidence: 99%

Drug Treatment of Hypertension: Focus on Vascular Health

Cameron

Lang

Touyz

2016

Drugs

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Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure elevation, the vascular system is particularly important, because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high blood pressure have greater efficacy for reducing cardiovascular risk than drugs that reduce blood pressure but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme Key Points• Hypertension is characterized by a vascular phenotype of endothelial dysfunction and structural remodeling.• Anti-hypertensive drugs that target the vascular changes associated with hypertension appear to be most efficacious• New anti-hypertensive drugs should promote vascular health as well as reducing blood pressure 3

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