Overektomize sıçanlarda hormon yerine koyma tedavisinin atorvastation ile konbinasyonunun kardiyovasküler sistem üzerindeki etkisinin araştırılması

Post menapozal kadinlarda ostrojen yoklugunun neden oldugu bazi metabolik vevaskuler degisikliklere bagli olarak kardiyovaskuler hastaliklarin ortaya cikma sikligiartmaktadir. Ostrojen yerine koyma tedavisi (OYT) lipid metabolizmasini ve endotelfonksiyonlari duzenleyerek kardiyoprotektif etkiler gostermektedir.Buna karsinendometriyal hiperplaziye neden olarak endometriyal kanser riskini artirmaktadir.OYT’ne progestinlerin eklenerek olusturulan hormon yerine koyma tedavisi (HYT)endometrial kanser riskini dusurmekte fakat lipid metabolizmasinda degisikliklermeydana getirerek EYT’nin kardiyoprotekif etkisini azaltmaktadir. Bu yuzdencalismamizda HRT ve hipolipidemik bir ajan olarak genis capli kullanim yeri olanatorvastatin (3-hidroksi 3-metil glutaril koenzim-A reduktaz inhibitoru)kombinasyonunu kullandik, HYT ve OYT tedavilerini overektomize sicanlarin genelozellikleri, vaskuler fonksiyonu bakimindan karsilastirarak bu tedavi rejimlerininkardioprotektif etkilerinde bir degisiklik olup olmadigini inceledik. OverektomizeWistar sicanlar dort gruba ayrilmistir. 1. Overektomize kontrol grup (OVX) 2.OYT’li grup (OVX+E) 3. HYT’li grup (OVX+E+P) ve 4. HYT + atorvastatintedavili grup (OVX+E+P+A). Tedavi rejimleri hayvanlara overektomi uygulandiktan10 gun sonra baslatilmis ve 10 hafta boyunca uygulanmistir. Bu sure sonunda butungruplarin beden agirliklari, kan basinclari, kan glukozlari, plazma lipid duzeyleri,ostrojen ve progesteron seviyeleri olculmustur. Cesitli agonistlerle inkube edilenizole torasik aorta preparatlarinda vaskuler reaktivite cevaplari isometrik olarakolculmustur. OVX grubunda beden agirliginda anlamli bir artis gozlenmistir. Kanbasinci ve glukozu bakimindan gruplar arasinda fark gozlenmemistir. Plazmaostrojen duzeyleri butun gruplarda artmis gozlenirken, progesteron duzeylerindedegisiklik gorulmemistir. KCL ve fenilefrin (FE) ile konsantrasyon yanit egrileridegerlendirildiginde, maksimum cevaplarin OVX grubunda artmis oldugugorulmustur. Kasilma yanitlarinda maksimum azalma ERT grubunda gozlenirken,diger iki tedavili grupta kasilma yanitlari daha az dusus gostermistir. Kalsiyumsuz veTH ile inkube edilen kalsiyumsuz ortamda FE ile kasilma yanitlarinin OYT grubundaanlamli azaldigi gozlenirken diger iki grupta anlamli dusus olmadigi gorulmustur.Bulgular L-NAME ile preinkubasyon yapilmis aort preparatlarinda butun gruplardakasilma yanitlarinin arttigini gostermektedir fakat en fazla artis OVX+E+P+Agrubunda gozlenmistir. Ayrica indometazinle preinkubasyon gruplar arasindaanlamli fark olusturmamistir. Fe ile onkastirma saglanan preparatlarda Ach ilegevseme yanitlarinda artis sirasiyla OVX+E, OVX+E+P+A, OVX+E+P gruplarindagozlenmistir. SNP ile ilde edilen gevseme yanitlari butun gruplarda benzerbulunmustur. Sonuclarimiz overektomize sicanlarda OYT’nin diger tedavirejimlerinden daha cok vaskuler fonksiyonlari iyilestirdigini gostermektedir.AbstractThe incidence of cardiovascular diseases in postmeapozal women is increased due to somemetabolic and vascular changes caused by deficiency of estrogen. Estrogen replacementtreatment (ERT) induced cardioprotective effect by regulating lipid metabolism andendothelium functions. However, it increases the risk of endometrial carcinoma by causingendometrial hyperplasia. Addition of progestin to ERT is called hormone replacementtreatment (HRT) and this treatment decreases the risk of endometrial carcinoma, but theatherogenic alterations in lipid metabolism decreases the cardioprotective effect of ERT.Because of these factors, in our study we used the combination of HRT with atorvastatin ( 3-hydroxy-3-methylglutaryl coenzim A reductase inhibitor), which is a widely usedhypolipodemic drug, HRT and ERT to compare each of these treatments in their effects ingeneral properties and vascular functions of ovariectomized rats to investigate whether thistreatment caused any change in cardioprotective effects. Ovariectomized Wistar rats aredivided into four groups. 1. Ovariectomized control group (OVX) 2.ERT group (OVX+E)3.HRT group (OVX+E+P) 4.HRT + atorvastatin group (OVX+E+P+A). Treatment is started10 days from the overiectomy and continued for 10 weeks. At the end, all the groups’ bodyweights, blood pressures, glucose, plasma lipid, estrogen and progesterone levels aremeasured. The vascular reactivity responses determined from isolated thorasic aortapreparations which are induced by various agonists are measured isometrically. A significantincrease in body weight of OVX group are observed. Differences in blood pressure andglucose measurements are not observed between groups. Plasma estrogen levels areincreased all of group with treatment but plasma progesterone levels are unchanged. WhenKCl and phenylephrine (Phe) cumulative concentration- response curves are evaluated, it isseen that maximum responses are increased in OVX group. The maximum decrease incontraction responses observed in ERT group, whereas a less decrease in contractionresponse occurred in two other groups. In Ca-free medium and thapsigargin preincubatedCa-free medium, it is observed that Phe contraction responses are decreased significantly inERT group and it is also determined that there is not a significant difference between othertwo groups . It is observed that L-NAME preincubation increased Phe-induced contractionresponses in all groups, besides the maximum increase is measured in OVX+E+P+A group.It is observed that indometacin preincubation made no statistical difference between groupsis not obtained. In preparations, of aorta with Phe precontracted, increased ACh-inducedrelaxation responses are observed in OVX+E, OVX+E+P+A ve OVX+E+P treatment groupsrespectively. Values of relaxation responses obtained by SNP were similiar in all of groups.Our results suggested that the ERT is better than other treatments in the improvement ofvascular functions in ovariecomized rats.