Pentaerythrityl tetranitrate attenuates structural changes in conduit arteries evoked by long-term NO-synthase inhibition.

Abstract

The aim of the study was to determine whether the pentaerythrityl tetranitrate (PETN), a tolerance devoid exogenous NO donor could prevent morphological changes in the cardiovascular system evoked by long-term NO-synthase inhibition. Three groups of 10-week-old Wistar rats were used: (1) controls, (2) treated by L-N(G)-nitroarginine methyl ester (L-NAME) in water (50 mg kg(-1)), and (3) treated by L-NAME (50 mg kg(-1) in water)+PETN (2x50 mg kg(-1), using gavage). Blood pressure (BP) was measured by the tail plethysmographic method. After sacrificing the animals were perfused (120 mmHg) by glutaraldehyde fixative and processed according to standard electron microscopy procedure. Wall thickness (WT), cross sectional area (CSA), inner diameter (ID) of thoracic aorta (TA), carotid (CA) and septal branch of the left descending coronary artery (RS) were measured in light microscopy. After 6 weeks, the BP was increased to 172+/-1.7 mmHg (P<0.01) in the L-NAME group, compared to 127+/-1.4 mmHg in controls. In L-NAME+PETN-treated rats, BP was 163+/-0.9 mmHg (P<0.01), and significantly lower (P<0.01) in comparison to L-NAME-treated rats. Heart weight and heart/body weight ratio was not significantly changed. In L-NAME-treated rats, both WT and CSA were increased in all three arteries (P<0.01). ID was increased only in TA (P<0.01). Wall/diameter ratio (WD) was increased in TA (P<0. 01) and CA (P<0.01). In L-NAME+PETN treated rats, WT was found to be increased only in TA (P<0.01). In comparison to the L-NAME treated group, WT was decreased in TA (P<0.01), in CA (P<0.01), in RS (P<0. 05). CSA was increased only in TA (P<0.01), yet in comparison to the L-NAME group it was decreased in CA (P<0.01). ID was increased in comparison to both control and L-NAME treated rats only in TA (P<0. 01). WD did not differ from the control value. In comparison to L-NAME-treated rats, it was decreased in both TA and CA (P<0.01). These data suggest that the changes in the cardiovascular system evoked by long-term NO-synthase inhibition were attenuated by simultaneous administration of the exogenous donor of nitric oxide - PETN.