Sex differences in endothelial function of aged hypertriglyceridemic rats – effect of atorvastatin treatment

Sotnikova, Ruzena; Bacova, Barbora; Vlkovicova, Jana; Navarova, Jana; Tribulova, Narcis

doi:10.2478/v10102-012-0025-2

Abstract

The aim of the study was to test the hypothesis that the effect of atorvastatin on endothelium-dependent relaxation of the superior mesenteric artery (SMA) may differ in male vs. female aged hypertriglyceridemic rats (HTGs). Experiments were performed on 11-month-old male and female Prague hereditary HTGs. Atorvastatin (ATO) was administered p.o. in the dose of 0.30 mg/100g/day.

Controls received vehiculum. After two months of ATO administration blood pressure, serum triglycerides (TG) and total cholesterol (CHOL) were determined. Endothelial function of SMA was studied in vitro using evaluation of relaxant responses of precontracted SMA to acetylcholine. The serum TG of control male HTGs were found to be statistically higher than those of female controls, while CHOL and blood pressure did not share gender differences. Responses of SMA of female control HTGs were statistically decreased compared to their male counterparts. ATO treatment induced decrease in blood pressure and TG of both males and females, yet CHOL values were reduced only in females. The protective effect of ATO on SMA endothelial function was much more pronounced in females compared to males.

We conclude that vascular endothelial dysfunction of aged HTG rats is more severe and more attenuated by ATO in females compared to males. The protective effect of ATO on vascular endothelial function does not seem to depend solely on its lipid lowering action.

References

Bacova B, Radosinska J, Knezl V, Kolenova L, Weismann P, Navarova J, Baran-cik M, Mitasikova M and Tribulova N. (2010). Omega-3 fatty acids and ator-vastatin suppress ventricular f brillation inducibility in hypertriglyceride-mic rat hearts: implication of intercellular coupling protein, connexin-43. J Physiol Pharmacol 61: 717-723.
Search in Google Scholar
Baños G, Medina-Campos ON, Maldonado PD, Zamora J, Pérez I, Pavón N and Pedraza-Chaverrí J. (2005). Antioxidant enzymes in hypertensive and hy-pertriglyceridemic rats: ef ect of gender. Clin Exp Hypertens 27: 45-57.
Search in Google Scholar
Celermajer DS. (1997). Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol 30: 325-333.10.1016/S0735-1097(97)00189-7
Search in Google Scholar
Gillespie CD, Keenan NL, Miner JB and Hong Y; Centers for Disease Control and Prevention (CDC). (2012). Screening for lipid disorders among adults-National Health and Nutrition Examination Survey, United States, 2005- 2008. MMWR Morb Mortal Wkly Rep 15 (Suppl): 26-31.
Search in Google Scholar
Gupta R, Sharma KK, Gupta A, Agrawal A, Mohan I, Gupta VP, Khedar RS and Guptha S. (2012). Persistent high prevalence of cardiovascular risk factors in the urban middle class in India: Jaipur Heart Watch-5. J Assoc Physicians India 60: 11 - 1 6 .
Search in Google Scholar
Libby P. (1995). Molecular bases of the acute coronary syndromes. Circulation 91: 2844-2850.
Search in Google Scholar
Liebermann EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, Yeung AC and Creager MA. (1994). Estrogen improves endothelium-dependent, f ow-mediated vasodilation in postmenopausal women. Ann Intern Med 121: 936-941.
Search in Google Scholar
Liu MY, Hattori Y, Fukao M, Sato A, Sakuma I and Kanno M. (2001). Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric arteries of female rats in long-term def ciency of oestrogen and during oestrus cycle. Br J Pharmacol 132: 1035-1046.
Search in Google Scholar
Lush CW, Cepinskas G and Kvietys PR. (2000). LPS tolerance in human endo-thelial cells: reduced PMN adhesion, E-selectin expression, and NF-kappaB mobilization. Am J Physiol Heart Circ Physiol 278: H853-H861.
Search in Google Scholar
Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, Bramucci E, Angoli L, Marsico F and Specchia G. (1993). Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 88: 358-363.
Search in Google Scholar
Mounier-Vehier C, Simon T, Guedj-Meynier D, Ferrini M, Ghannad E, Hubermann JP, Jullien G, Poncelet P, Achouba A, Quéré S and Guenoun M. (2012). Gender-related dif erences in the management of hypertension by cardiologists: the PARITE study. Arch Cardiovasc Dis 105: 271-280.
Search in Google Scholar
Pepine CJ, Nichols WW and Pauly D F. (2006). Estrogen and dif erent aspects of vascular disease in women and men. Circ Res 99: 459-461.
Search in Google Scholar
Pitsavos C, Skoumas I, Masoura C, Aznaouridis K, Papadimitriou L, Chryso-hoou C, Giotsas N, Toutouza M and Stefanadis C. (2008). Prevalence and determinants of coronary artery disease in males and females with familial combined hyperlipidaemia. Atherosclerosis 199: 402-407.
Search in Google Scholar
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). (1994). Lance 344: 1383 -1389.10.1016/S0140-6736(94)90566-5
Search in Google Scholar
Rosengren A, Wallentin L, Gitt AK, Behar S, Battler A and Hasdai D. (2004). Sex, age, and clinical presentation of acute coronary syndromes. Eur HeartJ 25: 663- 670.
Search in Google Scholar
Sacks FM, Pfef er MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR and Braunwald E. (1996). The ef ect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Tr i a l inv es t i gat o rs . New England J Med 335: 1001-1009.
Search in Google Scholar
Sakabe K, Fukuda N, Fukuda Y, Wakayama K, Nada T, Morishita S, Shinohara H and Tamura Y.(2008). Gender dif erences in short-term ef ects of atorvas-tatin on lipid prof le, f brinolytic parameters, and endothelial function. Nutr Metab Cardiovasc Dis 18: 182-188.
Search in Google Scholar
Sima AV, Stancu CS and Simionescu M. (2009). Vascular endothelium in atherosclerosis. Cell Tissue Res 335: 191-20 3.
Search in Google Scholar
Sudhir K, Jennings GL, Funder JW and Komesarof PA. (1996). Estrogen enhances basal nitric oxide release in the forearm vasculature in perimeno-pausal women. Hypertension 28: 330-334.
Search in Google Scholar
Truong QA, Murphy SA, McCabe CH, Armani A and Cannon CP; TIMI Study Group. (2011). Benef t of intensive statin therapy in women: results from PROVE IT-TIMI 22. Circ Cardiovasc Qual Outcomes 4: 328-336.
Search in Google Scholar
Vaughan CJ, Gotto AM Jr and Basson CT. (2000). The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 35: 1-10.
Search in Google Scholar
Xi H, Akishita M, Nagai K, Yu W, Hasegawa H, Eto M, Kozaki K and Toba K. (2007). Potent free radical scavenger, edaravone, suppresses oxidative stress-induced endothelial damage and early atherosclerosis. Atherosclerosis 191: 281-289.
Search in Google Scholar

Sex differences in endothelial function of aged hypertriglyceridemic rats – effect of atorvastatin treatment

Abstract

Paradigm

My account