title: Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects.
abstract: Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against NG-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5-20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.
authors.affiliation: Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France, casellas@iurc1.iurc.montp.inserm.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Casellas
authors.affiliation: Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Herizi
authors.affiliation: Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Artuso
authors.affiliation: Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Mimran
authors.affiliation: Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jover
keywords: arterial remodelling; cardiac hypertrophy; glomerular injury; interstitial fibrosis; vascular injury