Abstract
The incidence of cardiovascular disease among women during their reproductive years is considerably less than in men and this difference decreases after menopause. Since in cultured endothelial cells and in platelets E2 increases nitric oxide (NO) production, it is possible that their cardioprotective effect may be mediated by NO. The aim of this study was to evaluate platelet cyclic guanosine monophosphate (cGMP), as a marker of NO production, during menstrual cycle. Fifteen women aged 26–40 yr were studied to evaluate: LH, FSH, E2, P and cGMP on the 5th follicular and 22nd luteal day of the cycle and during the ovulatory period. Platelet cGMP was evaluated in basal condition (3-isobuthyl 1-methylxanthine- IBMX) and with ionomycine (IONO) and sodium nitroprusside (SNP). Results: LH, FSH, E2 and P demonstrated the typical patterns of ovulatory cycle. During follicular and luteal IBMX, SNP and IONO phase were homogeneous while they increased during the ovulatory period. A correlation between IBMX cGMP and E2 (p<0.002, rs=0.456) was found. In conclusion the data show an increase in platelet cGMP during the ovulatory period and a correlation between E2 and cGMP suggesting that E2 modulates NO production. The cardioprotective effect of E2 may be, at least in part, mediated by the increase in NO production.
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Lerner D.J., Kannel W.B. Patterns of coronary heart disease morbidity and mortality in the sexes: A 26-year of follow-up of the Framingham population. Am. Heart J. 1986, 111: 383–390.
Barret-Connor E., Bush T.L. Estrogen and coronary heart disease in women. J.A.M.A. 1991, 265: 1861–1867.
Wenger N.K., Speroff L., Packard B. Cardiovascular health and disease in women. N. Engl. J. Med. 1993, 329: 247–256.
Stampfer M.J., Willet W.C., Colditz G.A., Rosner B., Spiezer F.E., Hennekens C.H.N. A prospective study of menopausal estrogen therapy and coronary heart disease. N. Engl. J. Med. 1985, 313: 1044–1049.
Sarrel P.M. Ovarian hormones and the circulation. Maturitas 1990, 590: 287–298.
Notelovitz M. Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial. Am. J. Obstet. Gynecol. 1992, 167: 1255–1261.
Ernster V.L., Bush T.L., Hulka B.S., Kelsey J.L., Schottenfeld D. Clinical perspectives. Benefits and risks of menopausal estrogen and/or progestin hormone use. Prev. Med. 1988, 17: 201–223.
Lobo R.A. Estrogen replacement therapy and hypertension. Postgrad. Med. J. 1987, 14: 48–54.
Luscher T.F., Tanner F.C. Endothelial regulation of vascular tone and growth. Am. J. Hypertens. 1993, 6: 283S–293S.
Flier J.S., Underhill L.H. Platelet-endothelium interactions. N. Engl. J. Med. 1993, 328: 628–635.
Schray-Utz B., Zeiher A.M., Busse R. Expression of constitutive NO synthase in cultured endothelial cells is enhanced by 17β estradiol. Circulation 1993, 88: 180 (Abstract 0416).
Rosselli M., Imthurm B., Macas E., Keller P.J., Dubey R.K. Circulating nitrite/nitrate levels increase with follicular development: indirect evidence for estradiol mediated NO release. Biochem. Biophys. Res. Commun. 1994, 202: 1543–1552.
Nakano Y., Oshima T., Matsuura H., Kajiyama G., Kambe M. Effect of 17β-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis. Arterioscler. Thromb. Vasc. Biol. 1998, 18: 961–967.
Mistry D.K., Garland C.J. Nitric oxide (NO)-induced activation of large conductance Ca++-dependent K+ channels BK(Ca)) in smooth muscle cells isolated from the rat mesenteric artery. Br. J. Pharmacol. 1998, 124: 1131–1140.
Imthurn B., Rosselli M., Jaeger A.W., Keller P.J., Dubey R.K. Differential effects of hormone-replacement therapy on endogenous nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17\-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate. J. Clin. Endocrinol. Metab. 1997, 82: 388–394.
Yallampalli C., Byam-Smith M., Nelson S.O., Garfield R.E. Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus. Endocrinology 1994, 134: 1971–1974.
Ohshima N., Iwamoto T., Shigakawa M. Regulation of Ca2+ entry in rat aortic smooth muscle cells in primary culture. J. Biochem. 1994, 116: 274–281.
Cavallini L., Coassin M.G., Boaren A., Alexandre A. Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-triphosphate receptor and promote its phosphorilation. J. Biol. Chem. 1996, 27: 5545–5551.
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Martina, V., Bruno, G.A., Zumpano, E. et al. Platelet cyclic guanosine monophosphate production during menstrual cycle in healthy women. J Endocrinol Invest 25, 334–337 (2002). https://doi.org/10.1007/BF03344014
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DOI: https://doi.org/10.1007/BF03344014