Candesartan and progression of preglomerular lesions in N-G-nitro-L-arginine methyl ester hypertensive rats

Chronic administration of N-G-nitro-L-arginine methyl ester (L-NAME) to rat s induces systemic hypertension and progressive development of preglomerula r sudanophilic (SB+) lesions. This study investigates whether progression o f SB+ lesion formation from 4 to 6 wk of L-NAME treatment (20 mg/kg per d, orally) would be affected by 2 wk administration of either the angiotensin II type 1 receptor antagonist candesartan cilexetil (3 and 10 mg/kg per d) or the vasodilator hydralazine (15 mg/kg per d). Frequencies of arcuate art erial branches (ArcB), interlobular arteries (ILA), and afferent arterioles (AA) endowed with SB+ lesions were assessed on preglomerular vasculatures isolated after HCl maceration. Systolic BP (SBP, tail-cuff manometry) incre ased from a baseline of 125 +/- 2 to 185 +/- 4, and to 193 +/- 4 mmHg after 4 and 6 wk of L-NAME treatment, respectively. During the fourth- to sixth- week period, albumin excretion increased significantly from 3.7 +/- 1.1 to 52.5 +/- 22.4 mg/24 h. At that time, SB+ lesions affected 62 +/- 8, 61 +/- 8, and 13 +/- 4% of ArcB, ILA, and AA, respectively. Candesartan cilexetil dose dependently reduced SEP, albumin excretion, and lesion development. At the highest dose, SB+ lesions only affected 12 +/- 6, 15 +/- 7, and 1 +/- 1% of ArcB, ILA, and AA, respectively. Hydralazine similarly reduced SEP an d albumin excretion, although frequencies of SB+ lesions appeared less affe cted along ArcB and ILA. In conclusion, progression of preglomerular SB+ le sion formation during L-NAME hypertension can be prevented by angiotensin I I type 1 receptor blockade, partly through pressure-lowering effects.