Effect of chronic nitric oxide deficiency on angiotensin II-induced hypertrophy of rat basilar artery.
OBJECTIVE
Although in vitro studies suggest that nitric oxide has an inhibitory effect on cellular proliferation and migration, in vivo experiments failed to support this conclusion. The present study was designed to determine the effect of endogenous nitric oxide on angiotensin II-induced hypertrophy of small arteries in vivo.


METHODS
Angiotensin II (200 ng/kg per minute), alone or in combination with N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg per day), was administered for 2 weeks in normotensive rats. Basilar arteries were harvested, and their geometry was determined in perfused and pressurized conditions.


RESULTS
Angiotensin II increased media thickness, media-lumen ratio, and cross-sectional area of the arteries, confirming the presence of hypertrophic remodeling. The concomitant administration of L-NAME, an inhibitor of nitric oxide synthesis, prevented vascular hypertrophy. The remodeling of the basilar artery geometry in the combined treatment was of eutrophic nature, similar to that observed with the administration of L-NAME alone.


CONCLUSIONS
Our results suggest that endogenous nitric oxide does not inhibit angiotensin II-induced vascular hypertrophy in vivo. Nitric oxide may even be a necessary factor for hypertrophy to develop.
Moreau
P
P
Division of Cardiology, Cardiovascular Research, University Hospital, Bern, Switzerland.
Takase
H
H
d'Uscio
L V
LV
Lüscher
T F
TF
D000704:Analysis of Variance; D000804:Angiotensin II; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006984:Hypertrophy / Q000139:chemically induced* / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009929:Organ Size; D051381:Rats; D011921:Rats, Inbred WKY; D013599:Systole; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester