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

Abstract

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 ω -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.