Altered pressure-natriuresis in obese Zucker rats

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

Research output: Contribution to journalArticle

75 Citations (Scopus)

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±4.0 x 10-8, n=9) and blood pressure (119±3 mmHg) were greater than those in lean Zucker rats (LZ, 7.0±1.9 x 10-8 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.

Original languageEnglish
Pages (from-to)1470-1475
Number of pages6
JournalHypertension
Volume33
Issue number6
DOIs
Publication statusPublished - 1999 Jun

Keywords

  • Hypertension
  • Insulin resistance
  • Microdialysis
  • Natriuresis
  • Nitric oxide
  • Obesity
  • Troglitazone

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Altered pressure-natriuresis in obese Zucker rats'. Together they form a unique fingerprint.

  • Cite this

    Fujiwara, K., Hayashi, K., Matsuda, H., Kubota, E., Honda, M., Ozawa, Y., & Saruta, T. (1999). Altered pressure-natriuresis in obese Zucker rats. Hypertension, 33(6), 1470-1475. https://doi.org/10.1161/01.HYP.33.6.1470