[Beneficial effects of exogenous NO donors on morphologic changes induced by long-term administration of NO synthase...

Nitric oxide represents an important mediator which is involved in a variety of cardiovascular functions. The goal of this work was to study the effect of long term NO synthase inhibition on the structure of conduit arteries. The second objective of this work was to determine whether changes in conduit arteries evoked by long term NO synthase inhibition could be prevented by concomitant delivery of exogenous NO. Two independent experiments (A, B) were performed. Both consisted of three groups of 10-week-old Wistar rats: (1) controls, (2) treated by L-NC-nitroarginine methyl ester (L-NAME) in water (50 mg/kg), and (3) in experiment A treated by L-NAME (50 mg/kg in water) + pentaerythrityetetranitrate (PETN) (2 x 50 mg/kg, using gavage), (3) in experiment B treated by L-NAME (50 mg/kg in water) + molsidomine (2 x 50 mg/kg, using gavage). Blood pressure (BP) was measured in all groups by the tail plethysmogrphic method. After 6 weeks the rats were killed and perfused by the glutaraldehyde fixative under the pressure equal to the control systolic blood pressure of 120 mmHg. Thoracic aorta, carotid artery and coronary artery were processed according to the standard electron microscopy procedure. Wall thickness (WT), cross sectional area (CSA), and inner diameter (ID) of the arteries were measured in light microscopy. A significant increase in BP, WT, CSA and WT/ID ratio (all p < 0.01) were observed after L-NAME administration in arteries, except of WT/ID in the coronary artery in experiment A where the increase was not significant. ID changed not. Administration of PETN or molsidomine to L-NAME treated rats resulted in a significant decrease in BP, WT, and CSA. The decrease in WT/ID in coronary arteries was present however not significant in experiment A. The inner diameter was significantly increased only in the thoracic aorta in experiment A. In summary, long term NO synthase inhibition evoked considerable morphological changes in the arterial wall of conduit arteries. The replacement of endogenous NO deficiency using exogenous NO donors resulted in a considerably beneficial effect in all parameters studied. (Fig. 4, Ref. 54.)