EFFECTS OF AMLODIPINE ON SERUM TESTOSTERONE, TESTICULAR WEIGHT AND GONADO-SOMATIC INDEX IN ADULT RATS
AbstractBackground: Calcium ions are vital in many biological processes including hormonal secretion,mitosis, reproduction, fertility and regulation of gene expression. Thus, calcium antagonists who arefrequently prescribed for the cure of cardiovascular diseases may affect any of these physiologicalprocesses. Methods: This quasi experimental study was done at Army Medical College, Rawalpindifrom October 2007 to March 2008. Thirty male Sprague Dawley rats, purchased from National Instituteof Health, Islamabad were divided into group A (vehicle treated controls) and group B (amlodipinetreated). After receiving drug treatment for 50 days, all the rats were sacrificed. Serum was stored tomeasure testosterone by enzyme immunoassay technique. The testes were removed for measuringabsolute testicular weight and gonado-somatic index. Results: Serum testosterone, absolute testicularweight and gonado-somatic index were found to be significantly reduced in amlodipine treated rats.Conclusion: These results suggest that long term treatment with amlodipine might be associated withsignificant testicular regression and reduction in serum testosterone. Furthermore, since dihydopyridineantagonists are widely used in hypertension, our data may have some clinical implication in themanagement of infertility associated with hypertension.Keywords: adverse effects, calcium channel blocker, amlodipine, testosterone, testis, gonadosomatic index
Triggle DJ. Calcium channel antagonists: Clinical uses–Past,
present and future. Biochem Pharmacol 2007;74:1–9.
Benoff S. Voltage-dependent calcium channels in mammalian
spermatozoa. Front Biosci 1998;3:1220–40.
Nowak, R. Antihypertension drug may double as male
contraceptive. J NIH Res 1994;6:27–8.
Almaida SA, Teofilo JM, Franci JAA, Brentegani LG,
Carvalho TLL. Antireproductive effects of calcium channel
blocker amlodipine in male rats. Exp Toxicol Pathol
Albers MM, Johnson W, Vivian V, Jackson RD. Chronic use
of the calcium channel blocker nifedipine has no significant
effect on bone metabolism in men. Bone 1991;12:39–42.
Stepien O, Iouzalen L, Herembert T, Zhu DL, Marche P.
Amlodipine and vascular hypertrophy. Int J Cardiol
Tang J, Liu Z, Ren D, Wu C. Effect of amlodipine on the
growth of vascular smooth muscle cells of spontaneously
hypertensive rats. J Tongji Med Univ 1997;17(3):165–7.
Franca LR, Suescun MO, Miranda JR, Giovambattista A,
Perello M, Spinedi E, et al. Testis structure and function in a
nongenetic hyperadipose rat model at prepubertal and adult
ages. Endocrinology 2006;147(3):1556–63.
Weglarz L, Parfiniewicz B, Orchel A, Dzierzewicz Z.
Antiproliferative effects of inositol hexaphosphate and
verapamil on human colon cancer Caco-2 and HT-29 cells.
Acta Pol Pharm. 2006;63:443–5.
Mel'nikova NP, Timoshin SS. Effect of calcium channel
blocker verapamil on DNA synthesis and activity of nucleolar
organizer in cardiomyocytes of newborn albino rats. Bulletin of
Experimental Biology and Medicine, Biophysics and
Romeo JH, Dombrowski R, Kwak YS, Fuehrer S, Aron DC.
Hyperprolactinaemia and verapamil: prevalence and potential
association with hypogonadism in men. Clin Endocrinol
Morad F, Elsayed EM, Mahmoud SM. Inhibition of steroid sex
hormones release in rats by two calcium channel blockers.
Pharmacol Res 1997;35:177–80.
Bourguignon JP, Gerard A, Debougnoux G, Rose J,
Franchimont P. Pulsatile release of GnRH from the rat
hypothalamus in vitro: calcium and glucose dependency and
inhibition by superactive GnRH analogs. Endocrinology
Haisenleder DJ, Ferris HA, Shupnik MA. The calcium
component of gonadotropin releasing hormone stimulated
luteinizing hormone subunit gene transcription is mediated by
calcium/calmodulin dependent protein kinase type II.
Simanainen U, McNamara K, Davey RA, Zajac JD,
Handelsman DJ. Severe subfertility in mice with androgen
receptor inactivation in sex accessory organs but not in testis.
Endocrinology 2008; 149:3330–8.
Rehm S, White TE, Zahalka EA, Stanislaus DJ, Boyce RW,
Wier, P.J. Effects of food restriction on testis and accessory sex
glands in maturing rats. Toxicol Pathol 2008;36:687–94.
Faucher CJ, Berger M, Turckheim MD, Jean GVC. Effect of
preweaning under nutrition on testicular development in male
mice. International Journal of Andrology 2008;5:627–35.
Zindy F, Besten WD, Chen B, Rehg JE, Latres E, Barbacid M,
et al. Control of Spermatogenesis in Mice by the Cyclin DDependent Kinase Inhibitors p18Ink4c and p19Ink4d. Mol Cell
Corbier P, Kerdelhue B, Picon R, Roffi J. Changes in testicular
weight and serum gonadotropin and testosterone levels before,
during, and after birth in the perinatal rat. Endocrinology
Weinbauer GF, Behre HM, Fingscheidt U, Nieschlag E.
Human follicle-stimulating hormone exerts a stimulatory effect
on spermatogenesis, testicular size, and serum inhibin levels in
the gonadotropin-releasing hormone antagonist-treated
nonhuman primate (Macaca fascicularis). Endocrinology