Increased angiogenesis in portal hypertensive rats: role of nitric oxide.
Systemic and especially splanchnic arterial vasodilation accompany chronic portal hypertension. Different soluble mediators causing this vasodilation have been proposed, the strongest evidence being for nitric oxide (NO). No data exist if structural vascular changes may partly account for this vasodilatory state. Here, we developed a new in vivo quantitative angiogenesis assay in the abdominal cavity and determined if: 1) portal hypertensive rats show increased angiogenesis; and 2) angiogenesis is altered by inhibiting NO formation. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls (CON). During the index operation (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sutured in the mesenteric cavity. After 16 days, rings were explanted, embedded in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (Nomega-nitro-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number of ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.05; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in PVL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the beta-adrenergic blocker, propranolol, did not prevent angiogenesis either in PVL or CON rats in a separate set of experiments (data not shown). The conclusions drawn from this study are that: 1) rats with portal hypertension show increased angiogenesis; and 2) inhibition of NO formation significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes.
Sumanovski
L T
LT
Department of Research, University Hospital Basel, Basel, Switzerland.
Battegay
E
E
Stumm
M
M
van der Kooij
M
M
Sieber
C C
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D020007:Implants, Experimental; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D011433:Propranolol