Evaluation for antioxidant and renoprotective activity of olmesartan using nephrectomy rats.
Angiotensin II type 1 receptor blockers, which inhibit the rennin-angiotensin system, are used in the treatment of hypertension. In addition to their ability to lower blood pressure, these compounds have also been reported to protect organs, such as kidney and heart. Although the mechanisms of these protective effects are not fully understood, it is generally thought that their antioxidant effects likely play a role. The aim of the present study was to characterize the relationship between the antioxidant activity of olmesartan and its pharmacological actions such as renoprotective or blood pressure lowering effects, using 5/6 nephrectomy rats. In 5/6 nephrectomy rats, the potential antioxidant power, the ratio of oxidized to unoxidized albumin, as a marker of protein oxidation in blood, both systolic and diastolic blood pressure, plasma creatinine concentration, and amounts of protein excreted into the urine were significantly higher than the corresponding values for sham operated rats. However, olmesartan significantly suppressed these parameters within 8 weeks after oral administration in 5/6 nephrectomy rats. The oxidized albumin ratio was significantly decreased 4 weeks after the administration of olmesartan and these lower levels were maintained at 8 weeks. Furthermore, olmesartan improved radical scavenging activity of isolated albumin from rat plasma. Interestingly, a good correlation was found between the oxidized albumin ratios and renal function, whereas no correlation was found in the case of blood pressure. Based on those findings, we conclude that the antioxidant properties of olmesartan may be related to its renoprotective action rather than an antihypertensive effect.
Kadowaki
Daisuke
D
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Anraku
Makoto
M
Tasaki
Yuka
Y
Taguchi
Kazuaki
K
Shimoishi
Kazuki
K
Seo
Hakaru
H
Hirata
Sumio
S
Maruyama
Toru
T
Otagiri
Masaki
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D010919:Placebos; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D000975:Antioxidants; D007093:Imidazoles; D010919:Placebos; D012709:Serum Albumin; D013777:Tetrazoles; C437965:olmesartan; D003404:Creatinine