27 Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011 Mar; 155(1):27–32. DOI 10.5507/bp.2011.018 © L. Figueroa-Valverde, F. Diaz-Cedillo, M. Lopez-Ramos, E. Garcia-Cervera, K. Quijano, J. Cordoba CHANGES INDUCED BY ESTRADIOL-ETHYLENEDIAMINE DERIVATIVE ON PERFUSION PRESSURE AND CORONARY RESISTANCE IN ISOLATED RAT HEART: L-TYPE CALCIUM CHANNEL Lauro Figueroa-Valverde a *, Francisco Diaz-Cedillo b , Maria Lopez-Ramos a , Elodia Garcia-Cervera a , Karen Quijano a , Johani Cordoba a a Laboratorio de Investigacion en Ciencias Biologicas y Farmacoqiímica de la Facultad de Ciencias Quimico-Biologicas, Universidad Autonoma de Campeche, Av. Agustin Melgar, Col Buenavista C.P.24039 Campeche Cam., Mexico b Laboratorio de Quimica Organica de la Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Nacional. Prol. Carpio y Plan de Ayala s/n Col. Santo Tomas C.P. 11340, Mexico, D.F. E-mail: lauro_1999@yahoo.com Received: December 10, 2010; Accepted: February 9, 2011 Key words: Estradiol-ethylenediamine/Perfusion pressure/Coronary resistance/L-type calcium channel Aim. The present study was designed to investigate the effects of estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. Methods. The Langendorff model was used to measure perfusion pressure and coronary resistance changes in iso- lated rat heart after estradiol-ethylenediamine derivative alone and following compounds; tamoxifen (estrogen receptor antagonist), prazosin (alpha1 adrenoreceptor antagonist), metoprolol (selective beta1 receptor blocker), indomethacin (prostanglandin synthesis inhibitor) and nifedipine (L-type calcium-channel inhibitor). Results. The results show that estradiol-ethylenediamine derivative [10 –9 mmol] significantly increased perfusion pressure (p = 0.005) and coronary resistance (p = 0.006) in isolated rat heart. Additionally, the effect of estradiol- ethylenediamine on perfusion pressure [10 –9 to 10 –4 mmol] was only blocked in the presence of the L-type calcium- channel (nifedipine). Conclusions. These data suggest that the effect of estradiol-ethylenediamine on perfusion pressure and vascular coronary involves activation of the L-type calcium channel through a non-genomic molecular mechanism. INTRODUCTION High blood pressure contributes substantially to cardiovascular disease incidence and premature mor- tality 1–3 . Studies monitoring ambulatory blood pressure have shown that blood pressure is higher in men than in women of similar age 4,5 . In addition, experimental and clinical studies 6–8 have demonstrated that sex hormones may be associated with hypertension. Further, sex differ- ences in blood pressure regulation in humans have also been demonstrated in various animal models 9–11 . For ex- ample, male spontaneously hypertensive rats (SHR) have higher blood pressure than do females of similar age 12–14 . These data suggest that among others, estrogen levels may influence blood pressure. In this regard, there is evidence that estrogen replacement in ovariectomized rats reduces arterial pressure response to psychological stress and that these effects are mediated, at least in part by nitric oxide 15 . In addition, estrogens have been shown to protect trans- genic hypertensive rats by shifting the vasoconstrictor- vasodilator balance of the renin-angiotensin system and consequently induce change in blood pressure 16 . There are also studies which suggest that some estra- diol derivatives also induce changes in blood pressure as well; for example, Bonacasa et al 17 ., reported indicate that estradiol derivative (2-methoxyestradiol) attenuates hypertension in spontaneously hypertensive rats while 2-hydroxyestradiol was found to reduce blood pressure in an obese rat model 18 . The molecular mechanism of these two estradiol derivatives involves inhibition of en- dothelin-1 synthesis by means of an estrogen receptor- independent mechanism 19 . These data taken together show that estradiol and its derivatives induce changes in blood pressure; nevertheless, the cellular site and molecu- lar mechanisms involved are very confusing. Differences in the chemical structure of estradiol and its derivatives may be in part responsible. To test this, the present study was designed to investigate the effects of an estradiol de- rivative on perfusion pressure and coronary resistance in isolated rat hearts using the Langendorff model. To evaluate the molecular mechanisms involved, the follow- ing compounds were used as pharmacological tools for blocking various receptors; tamoxifen (estrogen receptor antagonist) (ref. 20 ), prazosin (α 1 adrenoreceptor antago- nist) (ref. 21 ), metoprolol (selective β 1 receptor blocker) (ref. 22 ), indomethacin (prostaglandin synthesis inhibitor) (ref. 23 ) and nifedipine (L-type calcium-channel inhibitor) (ref. 24 ).