Early treatment with olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats.

Abstract

BACKGROUND:

Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus.

METHODS:

OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7-25 weeks.

RESULTS:

OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters.

CONCLUSIONS:

This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes.

• Authors: Tadashi Sofue, Hideyasu Kiyomoto, Hiroyuki Kobori, Maki Urushihara, Yoko Nishijima, Kumiko Kaifu, Taiga Hara, Sachiko Matsumoto, Atsuhiko Ichimura, Hiroyuki Ohsaki, Hirofumi Hitomi, Hiroshi Kawachi, Melvin R Hayden, Adam Whaley-Connell, James R Sowers, Sadayoshi Ito, Masakazu Kohno, Akira Nishiyama
• Journal: American journal of hypertension (Am J Hypertens) Vol. 25 Issue 5 Pg. 604-11 (May 2012) ISSN: 1941-7225 [Electronic] United States
• PMID: 22318512 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• Blood Glucose
• Imidazoles
• Membrane Proteins
• Tetrazoles
• nephrin
• Hydrochlorothiazide
• Hydralazine
• Reserpine
• olmesartan

Topics

• Albuminuria (etiology, metabolism, prevention & control)
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Animals
• Antihypertensive Agents (therapeutic use)
• Blood Glucose (metabolism)
• Blood Pressure (physiology)
• Body Weight (physiology)
• Diabetes Mellitus, Type 2 (complications)
• Disease Models, Animal
• Hydralazine (therapeutic use)
• Hydrochlorothiazide (therapeutic use)
• Imidazoles (therapeutic use)
• Juxtaglomerular Apparatus (injuries, metabolism)
• Male
• Membrane Proteins (metabolism)
• Podocytes
• Rats
• Rats, Inbred OLETF
• Reserpine (therapeutic use)
• Tetrazoles (therapeutic use)