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 rats induces systemic hypertension and progressive development of preglomerular sudanophilic (SB+) lesions. This study investigates whether progression of SB+ lesion formation froin 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 arterial 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) increased 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 SBP, 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 SBP and albumin excretion, although frequencies of SB+ lesions appeared less affected along ArcB and ILA. In conclusion, progression of preglomerular SB+ lesion formation during L-NAME hypertension can be prevented by angiotensin II type 1 receptor blockade, partly through pressure-lowering effects.
Casellas
D
D
Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France. casellas@iurc1.iurc.montp.inserm.fr
Benahmed
S
S
Artuso
A
A
Jover
B
B
D000419:Albuminuria / Q000139:chemically induced; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D006830:Hydralazine; C077793:candesartan cilexetil; D019331:NG-Nitroarginine Methyl Ester