Gestational hypothyroidism-induced changes in L-type calcium channels of rat aorta smooth muscle and their impact on the responses to vasoconstrictors

Document Type : Original Article

Authors

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): Thyroid hormones play an essential role in fetal growth and maternal hypo-thyroidism which leads to cardiovascular deficiency in their offspring.  Considering this, we intended to investigate the impact of gestational hypothyroidism on offspring vascular contractibility and possible underlying mechanisms.
Materials and Methods: Hypothyroidism was induced in female rats by administration of 6-n-propyl-2-thiouracil in drinking water (0.02%) till delivery. The offspring aorta smooth muscle (without endothelium) contractile response to KCl (10-100 mM), KCl in the presence of nifedipine (10-4-10-1 µM), phenylephrine (10-9-10-6 M) and finally, phenylephrine and caffeine 100 mM in Ca2+-free Krebs were measured.   
Results: KCl and phenylephrine-induced contractions were considerably lower in gestational hypothyroid (GH) than euthyroid offspring. GH responded to nifedipine with less sensitivity than control. The GH and control groups produced almost equal contraction in respond to phenylephrine and caffeine in Ca2+-free Krebs. 
Conclusion: This study suggests that in hypothyroid offspring L-type Ca2+ channels are less functional, while intracellular Ca2+ handling systems are less modified by low levels of maternal thyroid hormones.

Keywords

References

References
1. Bertram CE. Animal models and programming of the metabolic syndrome. Br Med Bull 2001; 60:103-121.
2. Fowden AL, Forhead AJ. Endocrine mechanisms of intrauterine programming. Reproduction 2004; 127:515-26.
3. Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: Causes and consequences. Physiology 2006; 21:29-37.
4. Zahediasl S. Importance of thyroid hormones in intrauterine programming. Int J Endocrinol Metab 2010; 8:186-7.
5. Patel J, Landers K, Li H, Mortimer RH, Richard K. Delivery of maternal thyroid hormones to the fetus. Trends Endocrinol Metab 2011;22:164-70.
6. Danzi S, Klein I. Thyroid hormone and the cardiovascular system. Med Clin North Am 2012; 96:257-68.
7. van Tuyl M, Blommaart PE, de Boer PA, Wert SE, Ruijter JM, Islam S, et al. Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs. Dev Biol 2004; 272:104-17.
8. Khaksari M, Shafiee M, Ghasemi A, Asl SZ. Effect of orally administered propylthiouracil in pregnant and lactating rats on isolated aorta contractility of their adult male offspring. Med Sci Monit 2009; 15:BR123-7.
9. Sutandar M, Garcia-Bournissen F, Koren G. Hypothyroidism in pregnancy. J Obstet Gynaecol Can 2007; 29:354-6.
10. Sabio JM, Rodriguez-Maresca M, Luna JD, Garcia del Rio C, Vargas F. Vascular reactivity to vasoconstrictors in aorta and renal vasculature of hyperthyroid and hypothyroid rats. Pharmacology 1994; 49:257-64.
11. Sanders KM. Invited review: mechanisms of calcium handling in smooth muscles. J Appl Physiol 2001; 91:1438-49.
12. Stratton DB, Morrow RJ. Calcium mobilization and sensitivity in intact and triton skinned aorta from thyropathologic rats. Life Sci 1991; 48:2207-14.
13. Rahmani MA, Cheema IR, Sen S, Peoples B, Riley SR. The effect of hyperthyroidism and hypothyroidism on alpha 1- and alpha 2-adrenergic responsiveness in rat aortic smooth muscle. Artery 1987; 14:362-83.
14. Pantos C, Mourouzis C, Katramadou M, Saranteas T, Mourouzis I, Karageorgiou H, et al. Decreased vascular reactivity to alpha1 adrenergic stimulation in the presence of hypothyroid state: a part of an adaptive response? Int Angiol 2006; 25:216-20.
15. Gisbert R, Perez-Vizcaino F, Cogolludo AL, Noguera MA, Ivorra MD, Tamargo J, et al. Cytosolic Ca2+ and phosphoinositide hydrolysis linked to constitutively active alpha 1D-adrenoceptors in vascular smooth muscle. J Pharmacol Exp Ther 2003; 305:1006-14.
16. Brown L, Nankervis R, Kerr D, Sernia C. Adrenoceptor-mediated cardiac and vascular responses in hypothyroid rats. Biochem Pharmacol 1994; 47:281-8.
17. Noguchi A, Whitsett JA. Ontogeny of alpha                 1-adrenergic receptors in the rat myocardium: effects of hypothyroidism. Eur J Pharmacol 1982; 86:43-50.
18. Zhong H, Minneman KP. Alpha1-adrenoceptor subtypes. Eur J Pharmacol 1999; 375:261-76.
19. Guibert C, Ducret T, Savineau JP. Voltage-independent calcium influx in smooth muscle. Prog Biophys Mol Biol 2008; 98:10-23.
20. Watanabe H, Washizuka T, Komura S, Yoshida T, Hosaka Y, Hatada K, et al. Genomic and non-genomic regulation of L-type calcium channels in rat ventricle by thyroid hormone. Endocr Res 2005; 31:59-70.
21. Vetter R, Rehfeld U, Reissfelder C, Fechner H, Seppet E, Kreutz R. Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function            in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats. Am J Physiol Heart Circ Physiol 2011; 300:H943-50.
22. Kim D. Effect of Thyroid Hormone on slow Calcium channel function in cultured chick ventricular cells. J Clin Invest. 1987; 80:88-94.
23. Hawthron MH. Effect of thyroid status on beta-adrenoceptors and calcium channels in rat cardiac and vascular tissue. Naunyn Schmiedebergs Arch Pharmacol. 1988; 337:539-544.
24. Yu Z, Wang T, Xu L, Huang CX. Thyroid hormone increased L-type calcium channel mRNA expression and L-type calcium current of myocytes in rabbits. Biomed Mater Eng 2012; 22:49-55.
25. Narayanan CH, Narayanan Y, Browne RC. Effects of induced thyroid deficiency on the development of suckling behavior in rats. Physiol Behav 1982; 29:361-70.
26. Koromilas C, Liapi C, Zarros A, Stolakis V, Tsagianni A, Skandali N, et al. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities. Int J Dev Neurosci 2014; 35C:1-6.
27. Goodman JH, Gilbert ME. Modest thyroid hormone insufficiency during development induces a cellular malformation in the corpus callosum: a model of cortical dysplasia. Endocrinology 2007; 148:2593-7.
28. Gilbert ME, Sui L, Walker MJ, Anderson W, Thomas S, Smoller SN, et al. Thyroid hormone insufficiency during brain development reduces parvalbumin immunoreactivity and inhibitory function in the hippocampus. Endocrinology 2007; 148:92-102.
29. Ahmed OM, Abd El-Tawab SM, Ahmed RG. Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I. The development of the thyroid hormones-neurotransmitters and adenosinergic system interactions. Int J Dev Neurosci 2010; 28:437-54.
30. Amerion M, Tahajjodi S, Hushmand Z, Mahdavi Shahri N, Nikravesh MR, Jalali M. The effect of maternal thyroid disorders (hypothyroidism and hyperthyroidism) during pregnancy and lactation on skin development in wistar rat newborns. Iran J Basic Med Sci 2013; 16:665-74.
31. Karbalaei N, Ghasemi A, Hedayati M, Godini A, Zahediasl S. The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats. Exp Physiol 2014; 99:701-14.
32. Ghasemi A, Mehrazin F, Zahediasl S. Effect of
nitrate and L-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats. J Physiol Biochem 2013; 69:751-9.
33. Weber LP, Chow WL, Abebe W, MacLeod KM. Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. Br J Pharmacol 1996; 118:115-22.
34. McAllister RM, Grossenburg VD, Delp MD, Laughlin MH. Effects of hyperthyroidism on vascular contractile and relaxation responses. Am J Physiol 1998; 274:E946-53.
35. Gunasekera RD, Kuriyama H. The influence of thyroid states upon responses of the rat aorta to catecholamines. Br J Pharmacol 1990; 99:541-7.
36. Vargas F, Moreno JM, Rodriguez-Gomez I, Wangensteen R, Osuna A, Alvarez-Guerra M, et al. Vascular and renal function in experimental thyroid disorders. Eur J Endocrinol 2006; 154:197-212.
37. McFadzean I, Gibson A. The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 2002; 135:1-13.
38. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano K, Harada K, et al. Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev 1997; 49:157-230.
Iranian Journal of Basic Medical Sciences
Volume 18, Issue 2 - Serial Number 2
February 2015
Pages 172-179

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