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 (Nomega-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).


CONCLUSIONS
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.
Chang
Ching-Chih
CC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
Huang
Hui-Chun
HC
Wang
Sun-Sang
SS
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chieh
MC
Lee
Shou-Dong
SD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003097:Collateral Circulation / Q000502:physiology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D011168:Portal System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine