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). Na data exist if structural vascular changes may partly account for this vasod ilatory state. Here, we developed a new in vivo quantitative angiogenesis a ssay 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 ligati on (PVL). Sham-operated rats served as controls (CON), During the index ope ration (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sut ured in the mesenteric cavity, After 16 days, rings were explanted, embedde d in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (N-omega-nitr o-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number o f ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.0 5; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in P VL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the B-adrenergic blocker, propranolol, did not prevent angioge nesis 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 formatio n significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes.