Premium
Pravastatin administration does not induce detrimental effects on hemodynamics and collaterals of portal hypertensive rats
Author(s) -
Chang ChingChih,
Wang SunSang,
Huang HuiChun,
Lee JingYi,
Lee FaYauh,
Lin HanChieh,
Lee ShouDong
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2009.06170.x
Subject(s) - pravastatin , medicine , portal hypertension , hemodynamics , collateral circulation , portal venous pressure , vasodilation , arteriogenesis , endocrinology , cardiology , pharmacology , ischemia , cholesterol , cirrhosis
Background and Aims: The 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor can enhance endothelial nitric oxide synthase expression and induce vasodilatation. The vasodilatory effect may be detrimental to portal‐systemic collaterals due to aggravating the shunting degrees. The present study investigated the effects of pravastatin, a HMG‐CoA reductase inhibitor, on the collateral vascular responsiveness to endothelin‐1 (ET‐1) and portal‐systemic shunting in portal hypertensive rats. Methods: The partial portal vein‐ligated (PVL) rats received either pravastatin (25 mg/kg per day) or distilled water since 2 days prior to until 7 days after ligation. On the 8 th day following hemodynamic measurements, the collateral vascular responsiveness to ET‐1 was evaluated by an in situ collateral perfusion model. The shunting degrees of collaterals were evaluated by constructing vascular flow‐pressure curves and color microsphere study, respectively. PVL rats underwent pre‐incubation with: (i) Krebs solution (control); or Krebs solution plus (ii) 2 × 10 −5 M pravastatin; (iii) pravastatin + N ω ‐nitro‐L‐arginine (10 −4 M); and (iv) pravastatin + indomethacin (10 −5 M), followed by ET‐1 (10 −10 –10 −7 M) administration to evaluate the collateral vascular responsiveness. Results: In chronic study, pravastatin did not modify systemic and portal hemodynamics and collateral vascular responsiveness to ET‐1. The resistances of flow‐pressure curves and the microsphere study demonstrated similar shunting degrees between both groups. Furthermore, pravastatin pre‐incubation didn't reduce collateral perfusion pressure to ET‐1. Conclusion: Chronic pravastatin administration does not induce detrimental effects on hemodynamics and collaterals in PVL rats, nor does it influence the shunting degree. In addition, it does not modify the vasoconstrictive effect of ET‐1 on the collaterals of PVL rats.