HYPOREACTIVITY OF MESENTERIC RESISTANCE ARTERIES IN PORTAL HYPERTENSIVE RATS

Background/Aims: Hyporesponsiveness to constrictors in portal hyperten sion has shown to involve increased production of nitric oxide in larg e arteries in vitro, Small arteries (diameter 50-500 mu m) are partly responsible for peripheral resistance and probably have different regu latory mechanisms from large arteries. The purpose of this study was t o investigate the hyporeactivity of small mesenteric resistance arteri es in portal hypertensive rats and to determine the role of nitric oxi de and prostaglandins in this hyporesponsiveness. Methods: Third branc h mesenteric arteries from normal and portal hypertensive rats obtaine d by portal vein ligation were isolated and suspended in myographs for isometric tension recording, Reactivity to vasoconstrictors was asses sed by dose-responses to phenylephrine (Phe 10(-8) to 10(-3) M) and by potassium chloride (KCI 45 mM), Acetylcholine (Ach 10(-5) M) was admi nistered in pre-contracted KCI 45 mM arterial rings to evaluate endoth elium-dependent relaxation, Pre-incubations with N-nitro-L-arginine (L -NNA 10(-4) M, a specific inhibitor of nitric oxide synthase, or with indomethacin (10(-5) M), a specific inhibitor of cyclo-oxygenase, were performed to compare the individual roles of nitric oxide and prostag landins in KCI 45 mM-induced contractions. Results: Impaired responses to Phe (3731 +/- 851 mu N and 5971 +/- 745 mu N, respectively; p<0.05 ) and to KCI (2197 +/- 251 vs 2804 +/- 222 mu N, respectively; p<0.05) were observed in mesenteric resistance arterial rings from portal hyp ertensive rats compared to rings from normal rats, Ach-dependent relax ation did not significantly differ between normal (-25.7 +/- 5.1%) and portal hypertensive (-17.3 +/- 3.3%) rats. Indomethacin induced a sim ilar significant increase in KCI-induced contraction in normal (3472 /- 400 mu N) and portal hypertensive (3432 +/- 654 rats. Nitric oxide synthesis inhibition had no effect in normal rats (3032 +/- 368 mu N) but significantly increased KCI-induced contraction in portal hyperten sive rats (3331 +/- 551 mu N) Conclusion: These results demonstrate th e existence of a hyporesponsiveness to vasoconstrictors in small mesen teric resistance arteries of portal hypertensive rats, which seems to be due to increased production of nitric oxide.