Influence Of Estradiol And Progesterone On The Sensitivity Of Rat Thoracic Aorta To Noradrenaline

The aim of this study was to investigate the effects of low and high doses of estradiol, and of progesterone on the response to noradrenaline in rat thoracic aorta. Two weeks after bilateral ovariectomy, female rats received a s.c. injection of vehicle (corn oil, 0.1 mL/day), estradiol (10 μg/kg/day or 4 mg/kg/day) and/or progesterone (20 mg/kg/day), for eight days. On the ninth day, the rats were sacrificed and aortic rings, with or without endothelium, were used to generate concentration-response curves to noradrenaline. Aortic rings with intact endothelium from the high-dose (4 mg/kg/day) estradiol group were supersensitive to noradrenaline compared to the vehicle or low-dose (10 μg/kg/day) estradiol groups (pD2 values = 7.86±0.09, 7.30±0.11 and 7.35 ± 0.04, respectively). Endothelium-intact aortic rings from high-estradiol rats were supersensitive to noradrenaline when compared to vehicle-, progesterone- and progesterone + high-estradiol-treated rats (pD2 values = 7.77±0.12, 7.21±0.13, 6.93±0.04 and 7.22±0.18, respectively). There were no significant differences among the pD2 values for noradrenaline in aortic rings without endothelium. In conclusion, at high but not low doses, estradiol increased the sensitivity to noradrenaline and this was prevented by progesterone. Both of these effects were endothelium-dependent. © 2001 Elsevier Science Inc.688881888Waldron, I., Why do women live longer than men? (1976) Journal of Human Stress, 2, pp. 2-13Benetos, A., Rudnichi, A., Thomas, F., Safar, M., Guize, L., Influence of heart rate on mortality in a French population. Role of age, gender, and blood pressure (1999) Hypertension, 33, pp. 44-52Schillaci, G., Verdecchia, P., Borgioni, C., Ciucci, A., Porcellati, C., Early cardiac changes after menopause (1998) Hypertension, 32, pp. 764-769Swahn, E., The care of patients with ischaemic heart disease from a gender perspective (1998) European Heart Journal, 19, pp. 1758-1765Le Tran, Y., Fung, A., Forster, C., Role of gender and vascular endothelium in rat aorta response to 17β-estradiol (1997) Canadian Journal of Physiology and Pharmacology, 75, pp. 1393-1397Kushawaha, R.S., Female Sex steroid hormones and lipoprotein metabolism (1992) Current Opinion in Lipidology, 3, pp. 167-172Nascimento, C.A., Kauser, K., Rubanyl, G.M., Effect of 17β-estradiol in hypercholesterolemic rabbits with severe endothelial dysfunction (1999) American Journal of Physiology, 276, pp. H1788-H1794Nabulsi, A.A., Folsom, A.R., White, A., Patshc, W., Heiss, G., Wu, K.K., Szklo, M., Association of hormone-replacement therapy with various cardiovascular risk factors in post-menopausal women (1993) New England Journal of Medicine, 328, pp. 1069-1075Minshall, R.D., Stanczyk, F.Z., Miyagawa, K., Uchida, B., Axthelm, X., Novy, M., Hermsmeyer, H., (1998) Journal of Clinical Endocrinology and Metabolism, 83 (2), pp. 649-659Gisclard, V., Miller, V.M., Vanhoutte, P.M., Effect of 17β-estradiol on endothelium-dependent responses in the rabbit (1988) Journal of Pharmacology and Experimental Therapeutics, 244, pp. 19-22White, M.M., Zamudio, S., Stevens, T., Tyler, R., Lindenfeld, J., Leslie, K., Moore, L.G., Estrogen, progesterone, and vascular reactivity: Potential cellular mechanisms (1995) Endocrine Reviews, 16 (6), pp. 739-751Stumf, W.E., Sar, M., The heart: A target organ for estradiol (1977) Science, 196, pp. 319-321Ciocca, D.R., Roig, L.M., Estrogen receptors in human nontarget tissues: Biological and clinical implications (1995) Endocrine Reviews, 16 (1), pp. 35-62Knauthe, R., Diel, P., Hegele-Hartung, C., Engelhaupt, A., Fritzemeier, K.H., Sexual dimorphism of steroid hormone receptor messenger ribonucleic acid expression and hormonal regulation in rat vascular tissue (1996) Endocrinology, 137 (8), pp. 3220-3227Jiang, C.W., Sarrel, P.M., Lindsay, D.C., Poole-Wilson, P.A., Collins, P., Endothelium-independent relaxation of rabbit coronary artery by 17 β-estradiol in vitro (1991) British Journal of Pharmacology, 104, pp. 1033-1037Jiang, C.W., Sarrel, P.M., Lindsay, D.C., Poole-Wilson, P.A., Collins, P., Progesterone induces endothelium-independent relaxation of rabbit coronary artery in vitro (1992) European Journal of Pharmacology, 211, pp. 163-167Austin, C., Chess-Williams, R., The influence of 17-β-oestradiol and the natural oestrous cycle on α-adrenoceptor-mediated responses of the cardiovascular system in the rat (1995) Journal of Pharmacy and Pharmacology, 47, pp. 656-660Colucci, W.S., Gimbrone M.A., Jr., McLaughlin, M.K., Halpern, W., Alexander, R.W., Increased vascular catecholamine sensitivity and alpha-adrenergic receptor affinity in female and estrogen-treated male rats (1982) Circulation Research, 50, pp. 805-811Cheng, D.Y., Gruetter, C.A., Chronic estrogen alters contractile responsiveness to angiotensin II and norepinephrine in female rat aorta (1992) European Journal of Pharmacology, 215, pp. 171-176Gisclard, V., Flavahan, N.A., Vanhoutte, P.M., Alpha adrenergic responses of blood vessels of rabbits after ovariectomy and administration of 17 β-estradiol (1987) Journal of Pharmacology and Experimental Therapeutics, 240, pp. 466-470Dogterom, J., De Jong, W., Diminished pressor response to noradrenaline of the perfused tail artery of pregnant rats (1974) European Journal of Pharmacology, 25, pp. 267-269Perusquía, M., Hernández, R., Morales, A.M., Campos, M.G., Villalón, C.M., Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta (1996) General Pharmacology, 27 (1), pp. 181-185Mester, J., Baulieu, E., Effects of progesterone: Synergy and antagonism with oestrogens (1984) Trends in Biochemical Sciences, 9 (2), pp. 56-59Sutherland, R.L., Geynet, C., Binart, N., Catelli, M.G., Schmelck, P.H., Mester, J., Lebeau, M.C., Baulieu, E.E., Steroid receptors and effects of oestradiol and progesterone on chick oviduct proteins (1980) European Journal of Biochemistry, 107, pp. 155-164Miller, V.M., Vanhoutte, P.M., Progesterone and modulation of endothelium-dependent responses in canine coronary arteries (1991) American Journal of Physiology, 261, pp. R1022-R1027Carvalho, M.H.C., Scivoletto, R., Fortes, Z.B., Nigro, D., The role of endothelium in vascular reactivity (1989) Brazilian Journal of Medical and Biological Research, 22, pp. 533-545Bento, A.C., De Moraes, S., Effects of estrogen pretreatment of the spare α1-adrenoceptors and the slow and fast components of the contractile response of the isolated female rat aorta (1992) General Pharmacology, 23 (3), pp. 565-570Ford, S.P., Reynolds, L.P., Farley, D.B., Bhatnagar, R.K., Van Orden, E.E., Interaction of ovarian steroids and periarterial alpha 1-adrenergic receptors in altering uterine blood flow during the estrous cycle of gilts (1984) American Journal of Obstetrics and Gynecology, 150, pp. 480-484Kondo, K., Okuno, T., Eguchi, T., Yasui, T., Suzuki, H., Nagahama, S., Saruta, T., Vascular action of high dose estrogen in rats (1980) Endocrinologia Japonica, 27, pp. 307-313Salt, P.J., Inhibition of noradrenaline uptake2 in the isolated rat heart by steroids, clonidine and methoxylated phenylethylamines (1972) European Journal of Pharmacology, 20, pp. 329-340Bolego, O.C., Cignarella, A., Ruzza, R., Zaarour, C., Messi, E., Zanisi, M., Puglisi, L., Differential effects of low- and high-dose estrogen treatments on vascular responses in female rats (1997) Life Sciences, 60 (25), pp. 2291-2302Vedernikov, Y.P., Liao, Q., Jain, V., Saade, G.R., Chwalisz, K., Garfield, R.E., Effect of chronic treatment with 17β-estradiol and progesterone on endothelium-dependent and endothelium-independent relaxation in isolated aortic rings from ovariectomized rats (1997) American Journal of Obstetrics and Gynecology, 176, pp. 603-60