In vivo angiogenesis in normal and portal hypertensive rats: role of basic fibroblast growth factor and nitric oxide.
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.
Sieber
C C
CC
Division of Gastroenterology, University Hospital Basel, Switzerland.
Sumanovski
L T
LT
Stumm
M
M
van der Kooij
M
M
Battegay
E
E
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D019335:Nitroarginine; D009569:Nitric Oxide