[Effect of chronic inhibition of nitric oxide synthesis on vascular structure: remodeling or growth?].
Nitric oxide is an important regulator of vascular tone, as evidenced by the marked increase in blood pressure produced by the inhibition of its synthesis. Furthermore, nitric oxide may be implicated in the modulation of vascular growth, although in vitro and in vivo studies have provided conflicting results. The aim of this study is to determine the effects of chronic nitric oxide synthase inhibition, with or without antihypertensive treatment, on the structure of the basilar artery in the rat. Rats were treated for 6 weeks with N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) alone or in combination with verapamil (100 mg/kg/day) or with trandolapril (1 mg/kg/day). Untreated rats served as controls. The structure of perfused and pressurized basilar arteries were analyzed in vitro using a video dimension analyzer. Chronic L-NAME treatment increased systolic arterial pressure (229 +/- 5 vs 147 +/- 3 for controls; p < 0.05) and the media to lumen ratio of the basilar artery (0.22 +/- 0.02 vs 0.15 +/- 0.01 for controls; p < 0.05). This structural alteration was mainly due to remodeling (remodeling index: 76%), but not to growth (growth index: 8%, NS). The concomitant administration of verapamil and trandolapril prevented the increase in blood pressure (154 +/- 6 and 146 +/- 5 mmHg, respectively) and the structural changes produced by L-NAME (Media/lumen ratio: 0.15 +/- 0.01 and 0.14 +/- 0.01 mmHg, respectively). In fact, a positive correlation was observed between the media to lumen ratio and the systolic arterial pressure (r = 0.6; p < 0.001). The effect of the two antihypertensive treatments, as well as the correlation between the wall to lumen ratio and the arterial pressure, suggest that the remodeling of the basilar artery depends mainly on the elevation of arterial pressure with little contribution of the L-arginine pathway. Furthermore, the very small and non significant increase in the cross-sectional area of the basilar arteries from L-NAME-treated rats (growth index of 8%), suggest that nitric oxide does not play an important role in the modulation of normal cerebral vascular growth in vivo.
Moreau
P
P
Division de cardiologie, recherche cardiovasculaire, Hôpital universitaire, Berne, Suisse.
Takase
H
H
Küng
C F
CF
Lüscher
T F
TF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D024510:Muscle Development; D009130:Muscle, Smooth / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril; D009569:Nitric Oxide; D001120:Arginine; D014700:Verapamil; D019331:NG-Nitroarginine Methyl Ester
Effet de l'inhibition chronique de la synthèse du monoxyde d'azote sur la structure vasculaire: remodelage ou croissance?