Abstrakt
The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular
responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OCinduced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.
Keywords: Baroreflex, cardiac hypertrophy, hypertension, oral contraceptive, prostaglandins, indomethacin
Resume
Cette etude avait pour but d’investiguer les effets de la synthese/inhibition des prostagladins avec l’indomethacine sur la pression sangauine, frequence cardiaque, poids du cœur, electrolytes plasmatiques et les reponses cardiaques a la stimulation des barorecepteurs arterielles chez les rats femele traites avec OC. L’administration orale de l’oestrogene synthetisee, ethinyl oestradial combine avec la progesterone, Norgestrel pour di semaines augmentaient significativequement la pression sanguine, le poids cardiaque compare avec ceu dans le groupe Sain(contrôle).L’administration de l’indomethacineinhibait significativement l’augmentation de la pression sanguine, et sans effect sur le pois cardiaque induit par OC. La frequence cardiaque,les concentrations du sodium et potasium n’etaient pas affectees par OC et/ou le traitement a l’indomethacine. L traitement a l’OC n’alternait les presseurs sympathiques et des reponses tachycardiques causees par de decharge bilaterale des barorecepteurs carotidiens. Cependant, ces reponses etaient significativement attenuees par le traitement a l’indomethacine. Les resultats
demontraient que le modele des rats,l’OC induit une elevation de la pression sanguine developpe l’hypertropie cardiaque qui n’est pas associe au stimulation des barorecepteurs sympathiques. Le resultat que l’indomethacine prevent l’elevation de la pression sanguine induit par OC, mais pas associe a l’hypertropie cardiaque.Indiquant que la synthese des protagladins peut etre un determinant important de l’hypertension induit par OC.
Correspondence: Dr. L.A. Olatunji, Department of Physiology, College of Health Sciences, University of Ilorin, PMB 1515, Ilorin, Nigeria. E-mail: tunjilaw@unilorin.edu.ng, tunjilaw04 @yahoo.com
Bibliografia
World Health Organization. Cardiovascular disease, and steroid hormone contraception: Report of WHO Scientific Group. WHO Technical Report Series 1998; 877:1-89.
Tanis BC, van Den Bosch MAAJ, Kemmeren JM, Cats VM, Helmerhorst FM, Algra A, vander Graaf Y and Rosendaal FR. Oral Contraceptives and the risk of myocardial infarction. N Engl J Med. 2001; 345: 1787-1793.
Ahmed SB, Hovind P, Parving H, Rosing P, Price DA, Laffel LM, Lansang MC, Stevanovic R, Fisher NDL and Hollenberg NK. Oral Contraceptives, angiotesin-dependent renal vasoconstriction, and risk of diabetic nephropathy. Diabetes Care 2005; 28: 1988 -1994.
Olatunji LA and Soladoye AO. Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats. Pathophysiology 2008; 15: 221-226.
Olatunji LA and Soladoye AO. Oral contraceptive-induced high blood pressure is prevented by renin-angiotensin suppression in female rats not by sympathetic nervous system blockade. Ind J Exper Biol 2008; 46: 749-754.
Durand P, Prost M and Blache D. Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity. Arterioscler Thromb Vasc Biol 1997;17: 1939-1946.
Durand P and Blache D. Enhanced platelet thromboxane synthesis and reduced macrophage-dependent fibrinolytic activity related to oxidative stress in oral contraceptive-treated female rats. Atheroscler 1996; 121: 205-216.
Biegimayer C, Hofer G, Kainz C, Reinthaller A, Kopp B and Jamisch H. Concentrations of various arachidonic acid metabolites in menstrual fluid are associated with menstrual pain and are influenced by hormonal contraceptives. Gynecol Endocrinol 1995; 9(4): 307-312.
Lanfranchi PA and Somers VK. Arterial baroreflex function and cardiovascular variability: interactions and implications. Am J Physiol 2002; 283: R815-R826.
Minson CT, Halliwill JR, Young TM and Joymer MJ. Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives. Circ. 2000; 102: 1473 -1476.
Minson CT, Halliwill JR, Young TM and Joymer MJ. Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity and vascular transduction in young women. Circ 2000; 101: 862-868.
Smith WL, Marnett LJ and DeWitt DL. Prostaglandin and thromboxane biosynthesis. Pharmacol Ther 1991; 49:153-179.
Hintze TH, Messina EJ, Martin EG, Baez A and Kaley G. Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs. Proc Soc Exp Biol Med 1986; 181: 289-297
McDowell TS, Axtelle TS, Chaplean MW and Abboud FM. Prostaglandins in carotid sinus enhance baroreflex in rabbits. Am J Physiol 1989; 257: R445-R450.
Imperial TP and Petrullis AS. A meta-analysis of low-dose aspirin for prevention of pregnancy-induced hypertensive disease. JAMA 1991; 266: 260-264.
Jackson EK, Oates JA and Branch RA. Indomethacin decreases arterial blood pressure and plasma renin activity in rats with aortic ligation. Circ Res 1981; 49: 180-185.
Campbell WB, Jackson EK and Graham RM. Saralasin-induced renin release: Its blockade by prostaglandin synthesis inhibitors in the conscious rat. Hypertens 1979; 1: 637-642.
Cryer B and Feldman M. Cyclooxygenase-I and cyclooxygenase-2 selectivity of widely used non-steroidal anti-inflammatory drugs. Am J Med 1998; 104: 413-421.
Adegunloye BJ, Omoniyi JO, Owolabi OA, Ajagbonna OP, Sofola OA and Coker HAB. Mechanisms of the blood pressure lowering effect of the calyx extract of Hibiscus sabdariffa in rats. Afr J Med Med Sci 1996; 25: 235-238.
Roy S. Effects of smoking on prostacyclin formation and platelet aggregation in users of oral contraceptives. Am J Obstet Gynecol 1999; 180: S364-S368.
Garg SK. Serum prostaglandin F levels during menstrual cycle in women using oral contraceptives. Int J Clin Pharmacol Ther Toxicol 1983; 21(8): 431-432.
He XR, Wang W, Crofton JT and Share L. Effects of 17-estradiol on sympathetic activity and pressor response to phenylepherine in ovariectomised rats. Am J Physiol 1998; 275: R1202-R1208.
Heesch CM and Rogers RC (1995). Effects of Pregnancy and progesterone metabolites on regulation of sympathetic outflow. Clin Exp Pharmacol Physiol 1998; 22: 136-142.
Xie PL, Chapleau MW, McDowell TS, Hajduczok G and Abboud FM. Mechanism of decreased baroreceptor activity in chronic hypertensive rabbits: Role of endogenous prostanoids. J Clin Invest 1990; 86: 625-630.
Langman MJ. Ulcer complications and nonsteroidal anti-inflammatory drugs. Am J Med 1988; 84: 15-19.