Therapeutic effects of nitric oxide-donor isosorbide dinitrate on atherosclerosis-induced alterations in hemodynamics and arterial viscoelasticity are independent of the wall elastic component.
Whether the arterial elastic structures are involved in the beneficial effects of long-term treatment with organic nitrates on atherosclerosis-induced changes in hemodynamics and arterial wall viscoelastic properties, are case for angiotensin-converting enzyme (ACE) inhibitors, is not known. In the present study, atherogenic (A) diet, and isosorbide dinitrate (ISDN) (I) (60 mg Risordan LP, daily dose) were given concomitantly for 4 months to adult Pitman-Moore minipigs (A + I animals, n = 8), which were compared with A (n = 8) or control (C, n = 8) animals. Blood flow was investigated by hemodynamics in the hindlimb arterial bed; and wall rheology, histomorphometry and elastin; and desmosine (DES) and isodesmosine (IDE) contents in the abdominal aorta. Atherosclerosis prominently impaired the function of capacitance and resistance arteries, altered blood pressure contours, increased aortic stiffness and wall tension, and reduced parietal viscoelasticity through viscous component blunting. The treatment with ISDN significantly improved aortic pulsatility, arteriolar opposition to blood flow, and blood pressure (BP) contours by restoring, at least in part, the wall viscoelastic properties. However, there was no significant change in the area of the pressure-diameter curve hysteresis between the three animal groups. In contrast, ISDN reduced neither the cross-sectional area of lesions nor the losses in wall elastin content and had no influence on lipid accumulations in vessels and in the blood. The present results demonstrate that the beneficial hemodynamic and wall viscoelastic effects elicited by ISDN in atherosclerotic minipigs are not accounted for by therapeutic properties of the nitric oxide (NO) donor against alterations of elastic structures, but by the viscoelastic properties in the arterial wall.
Augier
T
T
CJF INSERM 94-01, Biochemistry Lahoratory, School of Pharmacy, Hospital La Timone, Marseille, France.
Bertolotti
C
C
Friggi
A
A
Charpiot
P
P
Barlatier
A
A
Bodard
H
H
Chareyre
C
C
Guillou
J
J
Luccioni
R
R
Garcon
D
D
Rolland
P H
PH
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D004548:Elasticity; D004549:Elastin / Q000032:analysis*; D006439:Hemodynamics / Q000187:drug effects*; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D013552:Swine; D013556:Swine, Miniature; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014783:Viscosity
D014665:Vasodilator Agents; D004549:Elastin; D002784:Cholesterol; D007548:Isosorbide Dinitrate