Prolonged inhibition of nitric oxide synthesis in Yoshida hyperlipidemic rat: aorta functional and structural properties.
To test whether inhibition of nitric oxide synthesis, associated with high levels of plasmatic lipids, can induce atherosclerotic lesions and phenotypic changes in smooth muscle cell composition in the aortic wall of an atherosclerotic-resistant species such as the rat, an inbred strain of hyperlipidemic Pittsburgh Yoshida rat was subjected to prolonged treatment (2 months) with the nitric oxide-synthase inhibitor L omega-nitro-arginine-methyl ester or with L-arginine. The two types of in vivo treatments were not able to modify in vitro aortic endothelium-mediated relaxation induced by acetylcholine or calcium-ionophore A-23187, the endothelium-independent sodium nitrite relaxation and the contractile response to serotonin. Histology and lipid infiltration of vascular specimens showed that L omega-nitro-arginine-methyl ester in vivo treatment did not induce any significant change in the aortic wall. Monoclonal antibodies to myosin isoforms and immunofluorescence procedures revealed the presence of an immature smooth muscle cell subpopulation in aortic specimens from saline-treated Pittsburgh Yoshida rats, whose expansion has been related in other species to atherogenesis. This peculiar cell phenotype disappeared in our animal model after prolonged L omega-nitro-arginine-methyl ester treatment. These data indicate that, despite interference with endothelium-mediated nitric oxide synthesis, atherosclerosis does not develop in this animal model and furnish for the first time a biological justification for atherogenesis resistance of rat, i.e., the lack of activation of an immature aortic smooth muscle cell population which in atherosclerosis-prone species is involved in lesion formation.
Chinellato
A
A
Department of Pharmacology, University of Padova, Italy.
Ragazzi
E
E
Pandolfo
L
L
Froldi
G
G
Caparrotta
L
L
Amore
B
B
Sartore
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001120:Arginine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006439:Hemodynamics; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007476:Ionophores / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007476:Ionophores; D008055:Lipids; D009569:Nitric Oxide; D012701:Serotonin; D000001:Calcimycin; D001120:Arginine; D019001:Nitric Oxide Synthase; D009218:Myosins; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester