Role of epoxyeicosatrienoic acid in splanchnic vasodilation in portal hypertension

Abstract

Objective To evaluate the role of epoxyeicosatrienoic acid (EETs) in the haemodynamic alterations of experimental cirrhosis, and its relationship with vascular contractile reactivity and calcium sensitivity of mesenteric arteries. Methods Twenty control rats and 40 rats with carbon tetrachloride (CCl4)-induced cirrhosis were studied. The plasma EETs in the mesenteric arteries was evaluated by enzyme linked immunosorbent assay (ELISA). Concentration-response curves to Norepinephrine (NE) and calcium (Ca2+ ) were evaluated in mesenteric arteries pre-incubated with indomethacin (indo), N (G)-nitro-L-arginine-methyl-ester (L-NAME), 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), ibetiotoxin (IbTx) and Glibenclamide before and after the epoxygenase inhibitor miconazole. pD2 was calculated. the activity of myosin light chain phosphatase (MLCP) and myosin light chain (MLC20) phosphorylation were observed. Results The plasma EETs in mesenteric arteries were increased more than that in control rats (P<0.01), and the activity of MLCP was increased, the MLC20 phosphorylation decreased; The NE and Ca2+ response were decreased in small mesenteric arteries. Indo, L-NAME, ODQ, IbTx and Glibenclamide blunted the response to NE and Ca2+ more in cirrhotic than that in control rats (P<0.05). Concentration-response curves to miconazole showed an increased NE and Ca2+ response in cirrhotic rats (P<0.05); the activity of MLCP was decreased, the MLC20 phosphorylation was increased by using miconazole. An increased plasma EETs were significantly correlated with NE-pD2, Ca2+ -pD2, the activity of MLCP and the MLC20 phosphorylation in mesenteric arteries. Conclusion The increased plasma EETs play a role in splanchnic vasodilation of PHT through regulating the response to NE and Ca2+ in mesenteric arteries. Key words: Hypertension portal; Splanchnic vasodilation; Epoxyeicosatrienoic acid; Calcium sensitivity; Vascular reactivity