BACKGROUND: Angiogenesis plays a pivotal role in many processes. Here, we studied whether angiogenesis to basic fibroblast growth factor (bFGF) in normal and portal hypertensive rats requires nitric oxide (NO). METHODS: To measure angiogenesis in vivo, two Teflon rings filled with collagen I (Vitrogen 100) were fixed in the mesenteric cavity at day 0, with 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(omega)-nitro-L-arginine (NNA; 3.3 mg/kg per day) to the drinking water. After 16 days, rings were explanted and embedded, and vessels were morphometrically 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 +/- 202, n = 9). Without stimulation, numbers of ingrown vessels were significantly (P < 0.05) higher in PVL compared to CON rats. NNA substantially inhibited 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 reverse 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-inhibited angiogenesis in PVL rats.
BACKGROUND: Angiogenesis plays a pivotal role in many processes. Here, we studied whether angiogenesis to basic fibroblast growth factor (bFGF) in normal and portal hypertensiverats requires nitric oxide (NO). METHODS: To measure angiogenesis in vivo, two Teflon rings filled with collagen I (Vitrogen 100) were fixed in the mesenteric cavity at day 0, with 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(omega)-nitro-L-arginine (NNA; 3.3 mg/kg per day) to the drinking water. After 16 days, rings were explanted and embedded, and vessels were morphometrically 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 +/- 202, n = 9). Without stimulation, numbers of ingrown vessels were significantly (P < 0.05) higher in PVL compared to CON rats. NNA substantially inhibited 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 reverse 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-inhibited angiogenesis in PVL rats.