CELLULAR-CHANGES INDUCED BY CHRONIC NITRIC-OXIDE INHIBITION IN INTACTRAT BASILAR ARTERIES REVEALED BY CONFOCAL MICROSCOPY

Background Cellular aspects of remodelling have not been investigated fully in intact vessels due to lack of appropriate methodology. Object ive To determine the cellular alterations induced by chronic inhibitio n of nitric oxide (NO) production in intact rat basilar arteries by co mbined use of perfusion myography and a laser scanning confocal micros cope. Methods Wistar-Kyoto rats were treated with 10 mg/kg per day N-G -nitro-L-arginine methyl ester (L-NAME) for 3 weeks. Basilar arteries from treated and age-matched Wistar-Kyoto rat controls were mounted on a perfusion myograph, stained with the nuclear dye Hoechst 33 342 and fixed under pressure. The segments were mounted on a slide and visual ized using the 364 nm line of a laser scanning confocal microscope. Me taMorph software was used to obtain optical sections from the vessel a nd for morphology determinations. Results L-NAME treatment induced hyp ertension (systolic blood pressure control 129.2 +/- 2.7 mmHg and SBP L-NAME treatment 176.3 +/- 5.2 mmHg, P < 0.001). Compared with control rat arteries, arteries from treated rats had a reduced lumen diameter , similar wall thickness and an increased wall : lumen ratio. L-NAME t reatment induced specific changes in adventitia, media and intima, nam ely an increase in number of adventitial cells and in adventitia thick ness, a reduction in number of smooth muscle cells with no change in m edia thickness and reductions in number of endothelial cells, size of nuclei and luminal surface area. Conclusions Hypertension induced by c hronic inhibition of NO production is associated with eutrophic remode lling of rat basilar artery. However, within this overall maintenance of constant volume, there are marked cellular changes in adventitia, m edia and intima. The separate contributions of inhibition of NO produc tion and hypertension to the remodelling process need to be elucidated . (C) Rapid Science Publishers ISSN 0263-6352.