The angiotensin-II (AT-II) receptor blocker olmesartan reduces renal damage in animal models of hypertension and diabetes.
The development of angiotensin receptor blockers (ARBs) has resulted in effective oral treatment for hypertension. One of the most recent members of this therapeutic class is olmesartan medoxomil (OM). The active metabolite, olmesartan, produces insurmountable AT1 receptor blockade and dose-dependently reduces BP. In both experimental and clinical studies, ARBs have been shown to exert renoprotective effects in addition to antihypertensive activity. In an SHR model of hypertensive renal injury, OM (3.0 and 10.0 mg/kg/day) dose-dependently reduced BP but also reduced urinary protein excretion by 65% and 75%, respectively (P < 0.05). Similar doses of OM, in a DOCA-salt hypertensive rat model, did not affect BP but reduced urinary protein excretion by 26% and 39% when compared to control hypertensive animals (P < 0.05). Hypertension is a major pathophysiological determinant of progressive arterial damage that can accelerate the development of diabetic nephropathy. At doses of 0.6 and 6.0 mg/kg/day, OM significantly reduces hypertension associated with type 2 diabetes. These doses of OM reduced BP and dose-dependently reduced proteinuria 31% and 76%, respectively, in hypertensive ZDF rats (P < 0.01). OM also reduced renocortical and renomedulla injury by 19% and 50% at doses of 0.6 and 6.0 mg/kg/day. The glomerular sclerosis index (GSI) was also reduced by 25% and 37% (P < 0.05). Thus, OM improves both functional and morphologic damage associated with diabetic nephropathy. These studies demonstrate that OM, a potent ARB, dose-dependently reduces BP and also provides a dose-related nephroprotective effect in animal models of diabetes. These studies show that the antihypertensive affect of OM is renoprotective but suggest that these renal benefits may also occur independently from a reduction in BP. A further evaluation of the effects of OM in diabetes is warranted.
Pugsley
Michael K
MK
Pharmacology, Forest Research Institute, Jersey City, NJ 07311, USA. Mchael.Pugsley@frx.comi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003900:Desoxycorticosterone; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000517:prevention & control*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011924:Rats, Zucker; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; D003900:Desoxycorticosterone; C437965:olmesartan