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 language | English |
|---|---|
| Pages (from-to) | 1470-1475 |
| Number of pages | 6 |
| Journal | Hypertension |
| Volume | 33 |
| Issue number | 6 |
| Publication status | Published - 1999 Jun |
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Keywords
- Hypertension
- Insulin resistance
- Microdialysis
- Natriuresis
- Nitric oxide
- Obesity
- Troglitazone
ASJC Scopus subject areas
- Internal Medicine
Cite this
Altered pressure-natriuresis in obese Zucker rats. / Fujiwara, Keiji; Hayashi, Koichi; Matsuda, Hiroto; Kubota, Eiji; Honda, Masanori; Ozawa, Yuri; Saruta, Takao.
In: Hypertension, Vol. 33, No. 6, 06.1999, p. 1470-1475.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Altered pressure-natriuresis in obese Zucker rats
AU - Fujiwara, Keiji
AU - Hayashi, Koichi
AU - Matsuda, Hiroto
AU - Kubota, Eiji
AU - Honda, Masanori
AU - Ozawa, Yuri
AU - Saruta, Takao
PY - 1999/6
Y1 - 1999/6
N2 - 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.
AB - 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.
KW - Hypertension
KW - Insulin resistance
KW - Microdialysis
KW - Natriuresis
KW - Nitric oxide
KW - Obesity
KW - Troglitazone
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UR - http://www.scopus.com/inward/citedby.url?scp=0033018804&partnerID=8YFLogxK
M3 - Article
VL - 33
SP - 1470
EP - 1475
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 6
ER -