Abstract
NG-Nitro-l-arginine methyl ester hydrochloride (L-NAME) is a non-specific nitric oxide (NO) inhibitor and it has been used to eliminate the role of NO in many studies like animal models for hypertension. In this study, we aimed to investigate whether lisinopril treatment has any biochemical and/or histopathological effect on rat liver tissue in a L-NAME-induced hypertension model. Forty-eight 6-weeks-old male Spraque–Dawley rats were used in the study. The animals used in the study were randomly divided into four equal groups. To induce hypertension, L-NAME was added to drinking water at a concentration of 600 mg/l and each rat was given 75 mg/kg/day of L-NAME for 6 weeks. Tail cuff systolic blood pressure (SBP) was measured at first, third, and sixth weeks. There was a significant difference between the experiment groups and controls. In only lisinopril given and L-NAME plus lisinopril administered groups, each rat was given 10 mg/kg of lisinopril for 6 weeks. At the end of the study, the animals were sacrificed. Blood and tissue samples were collected for biochemical and histopathological analysis. It has been observed that mean NO level was significantly decreased in L-NAME given group (p<0.05). Mean ALT levels were significantly increased in lisinopril and L-NAME plus lisinopril given groups, when compared with the control group (p<0.05). AST levels were in normal range in all groups (p>0.05). Hepatocyte degeneration was prominent in lisinopril given group, whereas mononuclear cell infiltration was significant in L-NAME given groups. Although the beneficial effects in L-NAME-induced hypertension treatment, lisinopril can lead to some unexpected results like hepatocyte degeneration, serum enzyme level elevation, and slight mononuclear cell infiltration.
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References
Noble TA, Murray KM (1988) Lisinopril: A nonsulfhydryl angiotensin converting enzyme inhibitor. Clin Pharm 7: 659–669
Hagley MT, Hulisz DT, Burns CM (1993) Hepatotoxicity associated with ACE inhibitors. Ann Pharmacother 27: 228–231
Schattner A, Kozak N, Friedman J (2001) Captopril-induced jaundice: Report of two cases and a review of 13 additional reports in the literature. Am J Med Sci 322: 236–240
Kocab MA, Coppola D, Hiotis S., Karl RC, Barthel JS (2000) Captopril-associated cholestasis complicating the management of pancreatic cancer. Surg Endosc 14: 680–681
Valle R, Carrascosa M, Cillero L, Perez-Castrillon JL (1993) Enalapril-induced hepatotoxicity. Ann Pharmacother 27: 1405
Jeserich M, Ihling C, Allgaier H, Berg PA, Heilmann C (2000) Acute liver failure due to enalapril. Herz 25: 689–693
Hillburn RB, Bookstaver D, Whitlock WL (1993) Comment Angiotensin-converting enzyme inhibitor hepatotoxicity: Further insights. Ann Pharmacother 27: 1142–1143
Droste HT, de Vries RA (1995) Chronic hepatitis caused by lisinopril. Neth J Med 46: 95–98
Larrey D, Babany G, Bernuau J, Andrieux J, Degott C, Pessayre D, Benhamou JP (1990) Fulminant hepatitis after lisinopril administration. Gastroenterology 99: 1832–1833
Nunes AC, Amaro P, Mac as F, Cipriano A, Martins I, Rosa A, Pimenta I, Donato A, Freitas D (2001) Fosinopril-induced prolonged cholestatic jaundice and pruritus: First case report. Eur J Gastroenterol Hepatol 13: 279–282
Grossman HJ, Grossman VL, Bhatal PS (1994) Intrahepatic vascular resistance in cirrhosis. In J Bosch, RJ Groszmann (Eds.) Portal Hypertension: Pathophysiology and Treatment. Blackwell Scientific Publications, London: 1–16
Gardiner SM, Compton AM, Kemp PA, Bennett T (1990) Regional and cardiac hemodynamic effects of NG-nitro-l-arginine methyl ester in conscious, Long Evans rats. J Cardiovasc Pharmacol 101: 625–631
Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S (1990) Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 101: 746–752
Gokcimen A, Aydın G, Karaöz E, Malas MA (2001) Effect of diclofenac sodium administration during pregnancy in the postnatal period. Fetal Diagn Ther 16: 417–422
Tsuhamato H, Towner J (1986) Ethanol – induced liver fibrosis in rats fed high – fat diet. Hepatolog 6: 814–822
Aydin G, Ozcelik N, Cicek E, Soyoz M (2003) Histopathologic changes in liver and renal tissues induced by Ochratoxin A and melatonin in rats. Hum Exp Toxicol 22: 383–391
Yeung E, Wong FS, Wanless IR, Shiota K, Guindi M, Joshi S, Gardiner G (2003) Ramipril-associated hepatotoxicity. Arch Pathol Lab Med 127: 1493–1497
Hurlimann R, Binek J, Oehlschlegel C, Hammer B (1994) Enalapril (Reniten)-associated toxic hepatitis. Schweiz Med Wochenschr 124: 1276–1280
Gonzalez de la Puente MA, Calderon E, Espinosa R, Rincon M, Varela JM (2001) Fatal hepatotoxicity associated with enalapril. Ann Pharmacother 35: 1492
Lunel F, Grippon P, Cadranel JF, Victor N, Opolon P (1987) Acute hepatitis after taking enalapril maleate (Renitec). Gastroenterol Clin Biol 11: 174–175
Jeserich M, Ihling C, Allgaier HP, Berg PA, Heilmann C (2000) Acute liver failure due to enalapril. Herz 25: 689–693
Ekelund K, Johansson C, Nylander B (1977) Effects of 16,16-dimethyl prostaglandin E2 on food-stimulated pancreatic secretion and output of bile in man. Scand J Gastroenterol 12: 457–460
Hagmann W, Denzlinger C, Kepler D (1984) Role of peptide leukotrienes and hepatobiliary elimination in endotoxic shock. Circ Shock 14: 223–225
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Gokcimen, A., Kocak, A., Kilbas, S. et al. Effect of lisinopril on rat liver tissues in L-NAME induced hypertension model . Mol Cell Biochem 296, 159–164 (2007). https://doi.org/10.1007/s11010-006-9310-8
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DOI: https://doi.org/10.1007/s11010-006-9310-8