title: Chronic inhibition of NO synthesis per se promotes structural intimal remodeling of the rat aorta.
abstract: OBJECTIVE
  We characterized, using histomorphometry and transmission and scanning electron microscopy, the intimal remodeling of the thoracic aorta of normocholesterolemic young rats chronically-treated with N(omega)-nitro-L-arginine methylester (L-NAME) and examined the question whether these changes were caused by the lack of NO per se or by the hypertension which L-NAME administration induces.
  
  
  METHODS
  Male Wistar rats were divided randomly into three sets: control group, standard diet/L-NAME-treated group, and standard diet/L-NAME + captopril-treated group.
  
  
  RESULTS
  The treatment of rats with L-NAME for 4 weeks resulted in increased blood pressure (by 32% at the end of the treatment) as compared with the control value and intimal remodeling comprising a continuous layer of enlarged endothelial cells with irregular nuclear and cytoplasmic contours, lying over a thickened layer of fibrocollagenous support tissue focally expanded with lymphomononuclear cells and mainly diffuse foci of smooth muscle cells. In addition, the NO synthase inhibition caused a marked thickened tunica intima (150% thicker than the control value) and a significantly augmented intima : media ratio (126% higher than the control value). On the other hand, captopril prevented hypertension in rats simultaneously treated with L-NAME as compared with controls, and induced intimal remodeling comprising the same qualitative changes as those observed in L-NAME-treated rats. The tunica intima of l-NAME + captopril-treated rats was moderately thickened (60% increase in comparison with that of controls and 65% thinner as compared with L-NAME-treated rats). In the same way, the mean intima : media ratio of rats concomitantly treated with L-NAME and captopril was moderately increased (45% more) as compared with controls and significantly lower in comparison with rats administered L-NAME alone (36% less).
  
  
  CONCLUSIONS
  Chronic inhibition of NO synthesis per se promotes structural intimal remodeling of the rat aorta, which is potentiated by L-NAME-induced hypertension. Most important, the present findings favor the idea that blockade of NO synthesis by causing intimal remodeling might be a primary cause, as individual biologic phenomenon, in the development of an atherosclerotic plaque.
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. marossi@fmrp.usp.br
authors.forename: M A
authors.initials: MA
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Colombini-Netto
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002216:Captopril / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002216:Captopril; D019331:NG-Nitroarginine Methyl Ester