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.
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 (Nω-nitro-L-arginine [NNA]), in rats with partial portal vein ligation. Mean arterial pressure was measured before the perfusion experiments.
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).
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.