ROLE OF NO IN FLOW-INDUCED REMODELING OF THE RABBIT COMMON CAROTID-ARTERY

Flow-induced changes in Vessel caliber tend to restore baseline wall s hear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in th e adaptive increase in artery diameter in response to a chronic increa se in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animal s by long-term administration of N-G-nitro-L-arginine-methyl ester (L- NAME) in drinking water given for 4 weeks. The remaining 8 animals ser ved as controls. Mean arterial blood pressure was not significantly al tered by L-NAME treatment (91+/-2 in control versus 98+/-3 mm Hg in L- NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animal s (106.1+/-10.7 versus 196.2+/-32.3 mL/min, P<.003). The diameter of t he flow-loaded left CCA also increased significantly in both groups co mpared with the right CCA (2.15+/-0.12 and 2.54+/-0.1 mm, respectively , P<.02), but the increase was less in the L-NAME-treated than the con trol group (3.24+/-0.09 and 4.64+/-0.17 mm, respectively, P<.0001). Th e diameter of the anastomosed veins was also increased but to a much l esser degree in L-NAME-treated animals than in controls (4.14+/-0.29 v ersus 7.94+/-0.51 mm, P<.0001). As a result of artery enlargement, WSS was normalized in the Bow-loaded left CCA of the control group (8.87/-0.77 dynes/cm(2)) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value be ing significantly increased (18.7+/-2.2 dynes/cm(2), P<.006). Moreover , a highly significant positive correlation between WSS and blood how was obtained in L-NAME-treated animals (r=.84, P<.0001). We also found remodeling of the artery wall, with a larger increase in the medial c ross-sectional area associated with an increased number of smooth musc le cells, in the control group compared with the L-NAME-treated group (0.75+/-0.09 versus 0.49+/-0.04 mm(2) and 4504+/-722 versus 2717+/-282 cells/mm(2), P<.03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As y et unidentified additional metabolic processes appear to be necessary for a complete regulatory response.