In vivo angiogenesis in normal and portal hypertensive rats: role of basicfibroblast growth factor and nitric oxide

Background: Angiogenesis plays a pivotal role in many processes. Here, we s tudied whether angiogenesis to basic fibroblast growth factor (bFGF) in nor mal and portal hypertensive rats requires nitric oxide (NO). Methods: To measure angiogenesis in vivo, two Teflon rings filled with coll agen I (Vitrogen 100((R))) were fixed in the mesenteric cavity at day 0, wi th one supplemented with bFGF (100 ng). Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls ( CON). The role of NO was tested by adding the NO formation antagonist N-ome ga-nitro-L-arginine (NNA; 3.3 md/kg per day) to the drinking water. After 1 6 days, rings were explanted and embedded, and vessels were morphometricall y counted. Results: bFGF significantly stimulated vessel formation per implant in CON rats (from 624 +/- 97 without stimulation to 1123 +/- 171, n = 11, P < 0.01 ), but not in PVL rats (from 1106 +/- 174 without stimulation to 1046 +/- 2 02, n = 9). Without stimulation, numbers of ingrown vessels were significan tly (P < 0.05) higher in PVL compared to CON rats. NNA substantially inhibi ted angiogenesis in both groups (P < 0.01). Vessel numbers were 202 +/- 124 for PVL (n = 5) and 197 +/- 14 for CON (n = 5) animals. bFGF did not rever se angiogenesis prevented by NNA (373 +/- 98 for PVL, 265 +/- 26 for CON, n = 5 per group, NS). Conclusions: NO formation inhibition diminishes both unstimulated and bFGF- stimulated angiogenesis in CON rats. Moreover, bFGF cannot rescue NNA-inhib ited angiogenesis in PVL rats. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.