title: Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone.
abstract: OBJECTIVE
  We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension.
  
  
  METHODS
  Six groups of male adult Wistar rats were investigated: controls after 4 and 7 weeks of experiment, rats treated with L-NAME for 4 weeks and three recovery groups: spontaneous-reversion (4 weeks L-NAME + 3 weeks placebo), spironolactone-induced reversion (4 weeks L-NAME + 3 weeks spironolactone) and L-arginine-induced reversion (4 weeks L-NAME+ 3 weeks L-arginine). Blood pressure was measured by tail-cuff plethysmography. Relative weight of the LV, myocardial fibrosis (based upon histomorphometry and hydroxyproline determination) and conjugated dienes in the LV and aortic cross-sectional area, inner diameter and wall thickness were determined. NO-synthase activity was investigated in the LV and aorta.
  
  
  RESULTS
  L-NAME administration induced hypertension, left ventricular hypertrophy (LVH), LV fibrosis, aortic thickening and diminution of NO-synthase activity in the LV and aorta. Reduction in blood pressure and regression of LVH were observed in all recovery groups, yet reduction in LV fibrosis and aortic thickening were not. NO-synthase activity was restored only in the L-arginine and spironolactone group.
  
  
  CONCLUSIONS
  In our study, the reversion of hypertension and LVH was not dependent on the restoration of NO-synthase activity. Moreover, LV fibrosis and aortic remodelling seem to be more resistant to conditions resulting in regression of LVH. Preserved level of fibrosis in the initial period of LVH regression might result in loss of structural homogeneity and possible functional alterations of the LV.
authors.affiliation: Institute of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic. ludo@lfuk.sk
authors.forename: L
authors.initials: L
authors.lastname: Paulis
authors.forename: J
authors.initials: J
authors.lastname: Matuskova
authors.forename: M
authors.initials: M
authors.lastname: Adamcova
authors.forename: V
authors.initials: V
authors.lastname: Pelouch
authors.forename: J
authors.initials: J
authors.lastname: Simko
authors.forename: K
authors.initials: K
authors.lastname: Krajcirovicova
authors.forename: A
authors.initials: A
authors.lastname: Potacova
authors.forename: I
authors.initials: I
authors.lastname: Hulin
authors.forename: P
authors.initials: P
authors.lastname: Janega
authors.forename: O
authors.initials: O
authors.lastname: Pechanova
authors.forename: F
authors.initials: F
authors.lastname: Simko
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001120:Arginine / Q000627:therapeutic use*; D005355:Fibrosis; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester