VASCULAR HYPOREACTIVITY PERSISTS DESPITE INCREASED CONTRACTILITY AFTER LONG-TERM ADMINISTRATION OF ISOSORBIDE DINITRATE IN PORTAL HYPERTENSIVE RATS

Background/Aims: Portal hypertension is associated with decreased vasc ular responsiveness to vasoconstrictors, which may contribute to the h yperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administr ation of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats. Methods: Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as cont rols. There were four animal groups for this study: portal vein ligati on-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) grou p, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dini trate (5 mg . kg(-1) . 12 h(-1) was given by gavage for 8 days startin g 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement. Res ults: Contractile responses to KCl (15-90 mM) and phenylephrine (10(-9 )-10(-4) M) were recorded, Both vascular reactivity and sensitivity we re significantly reduced in portal vein ligation rats as compared to S ham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contract ile responses to KCl and phenylephrine mere significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate tre atment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats, Conclusion: Our results show that long-term administration of isosorbide dinitrate enhanced vascul ar contractility in both portal vein ligation and Sham rats, but relat ive hyporeactivity persisted in portal vein ligation rats.