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Renal Hemodynamic and Autoregulation Abnormalities in Type 2 Diabetic Rats at Prediabetic and Diabetic Stages
Author(s) -
Hashimoto Seiji,
Kawata Tetsuya,
Kanji Yamada,
Mochizuki Toshio,
Koike Takao
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a335-a
Subject(s) - medicine , endocrinology , diabetic nephropathy , olmesartan , renal blood flow , blood pressure , hemodynamics , type 2 diabetes , diabetes mellitus , renal circulation , blood flow , angiotensin ii receptor type 1 , abdominal aorta , kidney , angiotensin ii , aorta
The mechanisms underlying the development and suppression of diabetic nephropathy are still not fully understood. Recent studies suggested that early angiotensin (Ang) II blockade might be an effective strategy for preventing the development of type 2 diabetic renal injury. 1) To examine the role of hemodynamics in the prediabetic stage, we determined the effect of the AT1 receptor antagonist (OLM; olmesartan 5mg/kg) on total (RBF), superficial (SBF), and deep renal cortical blood flow (DBF) in OLETF rats (Type 2 Diabetes rats) aged 11 weeks. Blood glucose levels were similar between OLETF and control LETO rats, while body weights were higher at this age in the OLETF rats. OLM caused a significant decrease in blood pressure of both groups, and no significant change in RBF. OLM significantly increased SBF of control LETO (from 594 ± 62 to 672 ± 71 PU; p<0.05), but had no significant effect on SBF in OLETF. In contrast, OLM had no effect on DBF in LETO, but improved DBF in OLETF (from 264 ± 37 to 309 ± 51 PU; p<0.05). 2) In OLETF at about 40 weeks age we assessed the effect of changes of renal perfusion pressure (RPP) on renal blood flow. Using a manual clamp on the abdominal aorta, we measured RBF, SBF and DBF in response to comparable reductions of RPP. Whereas SBF showed no significant change in both OLETF rats and LETO rats, DBF decreased significantly more in OLETF than LETO (OLETF 83.9 ± 1.7%, LETO 95.0 ± 3.4%, p<0.05). These findings strongly suggest the presence of abnormal renal hemodynamics, especially in the deep cortical region; OLM improved these abnormalities at the prediabetic stage.