Activity induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance
Keywords:
androsterone, flutamide, perfusion, vascular resistance, rats, Wistar.
Abstract
Introduction. Few data exist with respect to the effects of androsterone and their derivatives at cardiovascular level. In addition, the molecular mechanisms and cellular site of action of these androgens are still unclear.Objective. An evaluation was conducted on the effects induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance.
Materials and methods. The effects of both androsterone and hemisuccinate of androsterone on the perfusion pressure and vascular resistance in isolated rat hearts (Langendorff model) were evaluated.
Results. The results showed that: (1) the hemisuccinate of androsterone [10-9 M] increases the perfusion pressure and vascular resistance in comparison with the androsterone [10-9 M]; (2) the effect of androsterone-derivative [10-9 M-10-5 M] on perfusion pressure not was inhibited by indometacin [10-6 M]; (3) nifedipine [10-6 M] blocks the effects exerted by hemisuccinate of androsterone [10-9 M-10-5 M] on perfusion pressure; and (4) the effect of androsterone-derivative [10-9 M-10-5 M] on perfusion pressure in presence of flutamide [10-6 M] was inhibited.
Conclusions. The effects induced by androsterone and hemisuccinate of androsterone on the perfusion pressure and resistance vascular probably involve the interaction of steroid-receptor androgenic and, indirectly, activation of the calcium channel to induce variations in the perfusion pressure.
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References
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32. Figueroa-Valverde L, Díaz-Cedillo F, Tolosa L, Maldonado M, Ceballos G. Synthesis of pregnenolone-pregnenolone dimer via ring A-ting a connection. J Mex Chem Soc. 2006;50:42-5.
33. Institute of Laboratory Animal, Resources Commission on Life Sciences, National Research Council. Guide for the care and use of laboratory animals. Seventh edition. Washington, D.C.: National Academies Press; 1996. p. 1-240.
34. Neely J, Liebermeister H, Battersby E, Morgan H. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967;212:804-14.
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36. Mombouli J, Vanhoutte P. Endothelial dysfunction: a novel therapeutic target endothelial dysfunction: From physiology to therapy. J Mol Cell Cardiol. 1999;31:61-74.
37. Schork M, Morinelli A, Masuda A. Testosterone treatment enhances thrombosane A2 mimetic. Induced coronary artery vasoconstriction in guinea pigs. Eur J Clin Invest. 1994: 24(Suppl.1);50-2.
38. Pham T, Robinson R, Danilo P, Rosen M. Effects of gonadal steroids on gender-related differences in transmural dispersion of L-type calcium current. Cardiovasc Res. 2002;53:752-62.
39. Guo Z, Peter W, Benten M, Krücken J, Wunderlich F. Nongenomic testosterone calcium signaling, genotropic actions in androgen receptor-free macrophages. J Biol Chem. 2002;277:29600-7.
40. Reckelhoff J, Zhang H, Srivastava K, Granger J. Gender differences in hypertension in spontaneously hypertensive rats. Role of androgens and androgen receptor. Hypertension. 1999;34:920-3.
41. Er F, Michels G, Brandt M, Khan I, Haase H, Eicks M, et al. Impact of testosterone on cardiac L-type calcium channels and Ca2+ sparks: Acute actions antagonize chronic effects. Cell Calcium. 2007;41:467-77.
42. Wolff E, Ho W, Kwok R. The steroid-receptor complex. Some considerations based on sp2-hybrized systems. J Med Chem. 1964;7:77-89.
2. van den Hoogen P, Feskens E, Nagelkerke N, Menotti A, Nissinen A, Kromhout D. The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. N Engl J Med. 2000;342:1675-6.
3. Roeters van-Lennep J, Westerveld H, Willem D, Vander E. Risk factors for coronary heart disease: implications of gender. Cardiovasc Res. 2002;53:538-49.
4. Appel H, Weicker H. Ultrastructural and morphometric investigations on the effects of training and administration of anabolic steroids on the myocardium of guinea pigs. Int J Sports Med. 1983;4:268-74.
5. Gordon T, Kannel W. Premature mortality from coronary heart disease: the Framingham Study. J Am Med Assoc. 1971;215:1617-25.
6. Kentz M, Lugani K. Morbidity and mortality chartbook on cardiovascular, lung and blood diseases. Bethesda, MD: National Heart, Lung, and Blood Institute; 1992. p. 1-55.
7. Boysen G, Nyboe J. Incidence and risk factors for stroke in Copenhagen, Denmark. Stroke. 1988;19:1345-53.
8. Hippisley-Cox J, Pringle M, Crown N, Meal A, Wynn A. Sex inequalities in ischaemic heart disease in general practice: cross sectional survey. British Med J. 2001;322:832.
9. Rossouw J, Prentice R, Manson J, Wu L, Barad D, Barnabei V. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. J Am Med Assoc. 2007;297:1465-77.
10. Kannel G, Hjortland M, McNamara P. Menopause and risk of cardiovascular disease: the Framingham Study. Ann Intern Med. 1976;85:447-52.
11. Stampfer M, Colditz G, Willett W. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses’ Health Study. N Engl J Med. 1991;325:756-62.
12. Grodstein F, Manson J, Stampfer M. Postmenopausal hormone use and secondary prevention of coronary events in the Nurses’ Health Study: A prospective, observational study. Ann Intern Med. 2001;135:1-8.
13. Cauley J, Gutai J, Kuller L. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989;129:1120-31.
14. Liu P, Death A. Handelsman D. Androgens and cardiovascular disease. Endocr Rev. 2003;24:313-40.
15. Levy D, Kannell W. Cardiovascular risks: New insights for Framingham. J Am Heart. 1988;116:266-72.
16. Zumoff B, Troxler R, O’Connor J, Rosenfeld R, Kream J, Levin J. Abnormal hormone levels in men with coronary artery disease. Arteriosclerosis. 1982;2:58-67.
17. Carson P, McDonald L, Pickard S, Pilkington T, Davies B. Effects of clofibrate with androsterone (atromid) and without androsterone (atromid-S) on blood platelets and lipids in ischaemic heart disease. Brit Heart J. 1966;28:400-3.
18. Melentyev A. Psyological features of patients with ischaemic heart disease and coronary behavior type “A”. Arteriosclerosis. 2000;151:225-6.
19. Nestler J, Usiskin K, Barlascini C, Welty D, Clore J, Blackard W. Suppression of serum dehydroepiandrosterone sulfate levels by insulin: an evaluation of possible mechanisms. J Clin Endocrinol Metab. 1989;69:1040-6.
20. Ding A, Stallone J. Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. J Appl Physiol. 2001;91:2742-50.
21. Slowinska-Srzednicka J, Zgliczynski S, Soszynski P, Makowska A, Zgliczynski W, Srzednicki M, et al. Decreased plasma levels of dehydroepiandrosterone sulphate (DHEA-S) in normolipidaemic and hyperlipo-proteinaemic young men with coronary artery disease. J Intern Med. 1991;230:551-3.
22. Gray A, Feldman H, Mckinlay J, Longcope C. Age, disease, and changing sex hormone levels in middle-age men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991;73:1016-25.
23. Nestler J, Beer N, Jakubowicz D, Colombo C, Beer R. Effects of insulin reduction with benfluorex on serum dehydroepiandrosterone (DHEA), DHEA sulfate, and blood pressure in hypertensive middle-aged and elderly men. J Clin Endocrinol Metab. 1995;80:700-6.
24. Schunkert H, Hense H, Andus T, Riegger G, Straub R. Relation between dehydroepiandrosterone sulfate and blood pressure levels in a population-based sample. Am J Hypertens. 1999;12:1140-3.
25. Kawano H, Yasue H, Kitagawa A, Hirai N, Yoshida T, Soejima H, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003;88:3190-5.
26. Ceballos G, Figueroa L, Rubio I, García A, Martínez A, Yañez R. Acute and nongenomic effects of testosterone on isolated and perfused rat heart. J Cardiovasc Pharmacol. 1999;33:691-7.
27. Kontula K, Seppanen P, Duyne P, Bardin C, Janne O. Effect of a nonsteroidal antiandrogen, flutamide, on androgen receptor dynamics and ornithine decarboxylase gene expression in mouse kidney. Endocrinology. 1985;116:226-33.
28. Henry PD. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol. 1980;46:1047-58
29. Yamamoto T, Nozaki-Taguchi N. Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor.Brain Res. 1996;739:104-10.
30. Figueroa-Valverde L, Luna H, Castillo-Henkel C, Muñoz-García O, Morato-Cartagena T, Ceballos-Reyes G. Synthesis and evaluation of the cardiovascular effects of two, membrane impermeant, macromolecular complexes of dextran-testosterone. Steroids. 2002; 67: 611-9.
31. Figueroa-Valverde L, Díaz-Cedillo F, Diaz-Ku E, Camacho-Luis A. Effect induced by hemisuccinate of pregnenolone on perfusion pressure and vascular resistance in isolated rat heart. African J Pharm Pharmacol. 2009;3:234-41.
32. Figueroa-Valverde L, Díaz-Cedillo F, Tolosa L, Maldonado M, Ceballos G. Synthesis of pregnenolone-pregnenolone dimer via ring A-ting a connection. J Mex Chem Soc. 2006;50:42-5.
33. Institute of Laboratory Animal, Resources Commission on Life Sciences, National Research Council. Guide for the care and use of laboratory animals. Seventh edition. Washington, D.C.: National Academies Press; 1996. p. 1-240.
34. Neely J, Liebermeister H, Battersby E, Morgan H. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967;212:804-14.
35. Hocht C, Opezzo J, Gorzalczany S, Bramuglia G, Tiara C. Una aproximación cinética y dinámica de metildopa en ratas con coartación aórtica mediante microdiálisis. Rev Argent Cardiol. 1999;67:769-73.
36. Mombouli J, Vanhoutte P. Endothelial dysfunction: a novel therapeutic target endothelial dysfunction: From physiology to therapy. J Mol Cell Cardiol. 1999;31:61-74.
37. Schork M, Morinelli A, Masuda A. Testosterone treatment enhances thrombosane A2 mimetic. Induced coronary artery vasoconstriction in guinea pigs. Eur J Clin Invest. 1994: 24(Suppl.1);50-2.
38. Pham T, Robinson R, Danilo P, Rosen M. Effects of gonadal steroids on gender-related differences in transmural dispersion of L-type calcium current. Cardiovasc Res. 2002;53:752-62.
39. Guo Z, Peter W, Benten M, Krücken J, Wunderlich F. Nongenomic testosterone calcium signaling, genotropic actions in androgen receptor-free macrophages. J Biol Chem. 2002;277:29600-7.
40. Reckelhoff J, Zhang H, Srivastava K, Granger J. Gender differences in hypertension in spontaneously hypertensive rats. Role of androgens and androgen receptor. Hypertension. 1999;34:920-3.
41. Er F, Michels G, Brandt M, Khan I, Haase H, Eicks M, et al. Impact of testosterone on cardiac L-type calcium channels and Ca2+ sparks: Acute actions antagonize chronic effects. Cell Calcium. 2007;41:467-77.
42. Wolff E, Ho W, Kwok R. The steroid-receptor complex. Some considerations based on sp2-hybrized systems. J Med Chem. 1964;7:77-89.
How to Cite
1.
Figueroa L, Díaz F, Camacho A, Díaz E, Marvin R. Activity induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance. Biomed. [Internet]. 2009 Dec. 1 [cited 2026 Mar. 6];29(4):625-34. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/140
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2009-12-01
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