Blunted Response of the Renin-Angiotensin System and Nitric Oxide Synthesis Related to Sodium Sensitivity in Immunoglobulin A Nephropathy

Konishi, Yoshio; Morikawa, Takashi; Yasu, Takanori; Teramoto, Kae; Okada, Noriyuki; Yoshioka, Katsunobu; Okumura, Michiaki; Imanishi, Masahito

doi:10.1291/hypres.27.7

Cited by 11 publications

(8 citation statements)

References 21 publications

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“…15 Similar results have also been reported in Dahl salt-sensitive hypertensive rats, 16 which show reduced intrarenal NO levels. 5 The present finding that patients with type 2 diabetic nephropathy display reduced urinary excretion of NOx and increased salt sensitivity of BP, combined with results from previous studies, 2,4,7,9,15,16 is consistent with the concept that salt sensitivity of BP is induced by decreased intrarenal NO bioactivity in patients with diabetic nephropathy. We observed that treatment with an ARB restored reduced urinary renal NOx excretion in patients with type 2 diabetic nephropathy and microalbuminuria.…”

Section: Discussionsupporting

confidence: 90%

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Imanishi

Okada

Konishi

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction:We have previously demonstrated the increased salt sensitivity of blood pressure (BP) in diabetic patients with early nephropathy. Here, we examined the effects of an angiotensin II receptor blocker (ARB) on salt sensitivity and renal oxidative stress or nitric oxide (NO) in those patients. Patients and methods: Type 2 diabetic patients with (n = 6) and without (n = 6) microalbuminuria were studied on a high-salt diet for one week and on a salt-restricted diet for one week. The study was repeated in the patients with microalbuminuria during treatment with an ARB, valsartan (80 mg/day). Salt sensitivity was assessed from the BP/sodium excretion curve. Urinary excretion rates of NOx, 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress, and plasma tetrahydrobiopterin as a cofactor for NO synthase were measured. Results: Compared with diabetic patients without microalbuminuria, patients with microalbuminuria showed greater salt sensitivity and lower urinary excretion of NOx. In the patients with microalbuminuria, treatment with valsartan reduced salt sensitivity in association with increased NOx excretion, reduced 8-hydroxy-2,-deoxyguanosine excretion, and increased plasma tetrahydrobiopterin levels. Conclusions: These data support the hypothesis that ARBs reduce the salt sensitivity of BP by decreasing renal oxidative stress and restoring NO activity in diabetic patients with microalbuminuria.

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Section: Discussionsupporting

confidence: 90%

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Imanishi

Okada

Konishi

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…Benign nephrosclerosis may be superimposed with IgAN. Hypertension is a well known risk factor for renal prognosis (4,5,(22)(23)(24). In our study, we histopathologically showed that vascular lesions, rather than mesangial cell proliferation, play an important role in glomerular sclerosis.…”

Section: Discussionsupporting

confidence: 51%

Impact of Hypertension and Hypertension-Related Vascular Lesions in IgA Nephropathy

et al. 2006

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“…The study was finally composed of 41 patients, including 35 who we had studied previously. 16 Table 1 shows the baseline characteristics of the patients.…”

Section: Methodsmentioning

confidence: 99%

Relationship Between Urinary Angiotensinogen and Salt Sensitivity of Blood Pressure in Patients With IgA Nephropathy

et al. 2011

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We demonstrated previously that the blood pressure of patients with IgA nephropathy becomes salt sensitive as renal damage progresses. We also showed that increased urinary angiotensinogen levels in such patients closely correlate with augmented renal tissue angiotensinogen gene expression and angiotensin II levels. Here, we investigated the relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy. Forty-one patients with IgA nephropathy consumed an ordinary salt diet (12 g/d of NaCl) for 1 week and a low-salt diet (5 g/d of NaCl) for 1 week in random order. The salt-sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linking 2 data points obtained during consumption of each diet. The urinary angiotensinogen:creatinine ratio was significantly higher in patients who consumed the ordinary salt diet compared with the low-salt diet (17.5 μg/g [range: 7.3 to 35.6 μg/g] versus 7.9 μg/g [range: 3.1 to 14.2 μg/g] of creatinine, respectively; P<0.001). The sodium sensitivity index in our patients positively correlated with the glomerulosclerosis score (r=0.43; P=0.008) and changes in logarithmic urinary angiotensinogen:creatinine ratio (r=0.37; P=0.017) but not with changes in urinary protein excretion (r=0.18; P=0.49). In contrast, changes in sodium intake did not alter the urinary angiotensinogen:creatinine ratio in patients with Ménière disease and normal renal function (n=9). These data suggest that the inappropriate augmentation of intrarenal angiotensinogen induced by salt and associated renal damage contribute to the development of salt-sensitive hypertension in patients with IgA nephropathy.

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Blunted Response of the Renin-Angiotensin System and Nitric Oxide Synthesis Related to Sodium Sensitivity in Immunoglobulin A Nephropathy

Cited by 11 publications

References 21 publications

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy

Impact of Hypertension and Hypertension-Related Vascular Lesions in IgA Nephropathy

Relationship Between Urinary Angiotensinogen and Salt Sensitivity of Blood Pressure in Patients With IgA Nephropathy

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