Involvement of constitutive nitric oxide synthase in the portal-systemic collaterals of portal hypertensive rats

Background: Recent studies have shown that endothelial nitric oxide (NO) is involved in modulating the vascular response to vasoconstrictors in portal-systemic collaterals of portal hypertensive rats. This study investigated which isoform of NO synthase is involved in the collateral circulation of portal hypertensive rats. Methods: The relaxation response to acetylcholine (10^-8 M, 10^-7 M and 10^-6 M) in norepinephrine (NE)-preconstricted portal-systemic collaterals was investigated after incubation with vehicle (Krebs solution), a preferential inducible NO synthase inhibitor (aminoguanidine [AG]), or a non-selective NO synthase inhibitor (N^ω-nitro-L-arginine [NNA]), in rats with partial portal vein ligation. Mean arterial pressure was measured before the perfusion experiments. Results: Bodyweight and mean arterial pressure before the perfusion studies were similar in the vehicle, AG and NNA groups. Preincubation with NNA, but not AG, produced a significant increase in baseline perfusion pressure compared with the vehicle group (p < 0.05). The increase in perfusion pressure in response to NE was enhanced in the presence of NNA (p < 0.05), but not AG. In addition, preincubation with NNA, but not AG, significantly suppressed acetylcholine-induced relaxation in the portal-systemic collaterals (p < 0.05). Conclusion: These results suggest that constitutive, rather than inducible, NO synthase is involved in the vascular response to vasoconstrictors in the portal-systemic collaterals of portal hypertensive rats.