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(Hypertension. 1999;33:1470-1475.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Altered Pressure-Natriuresis in Obese Zucker Rats

Keiji Fujiwara; Koichi Hayashi; Hiroto Matsuda; Eiji Kubota; Masanori Honda; Yuri Ozawa; Takao Saruta

From the Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

Correspondence to Takao Saruta, Professor of Medicine, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail saruta{at}mc.med.keio.ac.jp

Abstract—It has not been examined whether the pressure-natriuresis response is altered in the insulin-resistant condition. Furthermore, despite an important role of nitric oxide (NO) in modulating pressure-natriuresis, no investigations have been conducted assessing the renal interstitial NO production in insulin resistance. The present study examined whether pressure-natriuresis was altered in insulin-resistant obese Zucker rats (OZ) and assessed the cortical and medullary nitrate/nitrite (NOx) levels with the use of the renal microdialysis technique. In OZ, serum insulin/glucose ratio (23.0±4.0x10^-8, n=9) and blood pressure (119±3 mm Hg) were greater than those in lean Zucker rats (LZ; 7.0±1.9x10^-8 and 103±4 mm Hg, n=9). The pressure-natriuresis curve in OZ was shifted to higher renal perfusion pressure (RPP), and the slope was blunted compared with that in LZ (0.073±0.015 vs 0.217±0.047 µEq/min kidney weight/mm Hg, P<0.05). The basal renal NOx level was reduced in OZ (cortex, 4.032±0.331 µmol/L; medulla, 4.329±0.515 µmol/L) compared with that in LZ (cortex, 7.315±1.102 µmol/L; medulla: 7.698±0.964 µmol/L). Furthermore, elevating RPP increased the medullary NOx in LZ, but this pressure-induced response was lost in OZ. Four-week treatment with troglitazone, an insulin-sensitizing agent, improved hyperinsulinemia, systemic hypertension, and basal renal NOx levels (cortex, 5.639±0.286 µmol/L; medulla, 5.978±0.284 µmol/L), and partially ameliorated the pressure-natriuresis curves; the slope of pressure-natriuresis curves and elevated RPP-induced NOx, however, were not corrected. In conclusion, our study suggests that insulin resistance is closely associated with abnormal pressure-natriuresis and hypertension. These deranged renal responses to insulin resistance are most likely attributed to impaired medullary NO production within the medulla.

Key Words: natriuresis • nitric oxide • insulin resistance • hypertension • troglitazone • microdialysis • obesity

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