Expression of the alpha1a and alpha2A adrenergic receptor genes in myocardial and kidney tissues of hypertensive ISIAH rats

Myocardial and kidney levels of alpha1A and alpha2A adrenergic receptor mRNA have been examined in hypertensive ISIAH and normotensive WAG rats of 1.5 and 7 months of age using real-time PCR. Decreased levels of α_2A-AR mRNA in kidneys of both age groups of ISIAH rats have been found. In addition, an increased expression of the alpha1А adrenergic receptor gene in the kidneys of 7‑month-old ISIAH rats has been revealed. This profile of the renal expression of the α-adrenoreceptor genes in the hypertensive ISIAH rats is indicated as being associated with the increase of sympathetic stimulation of the kidneys and with development and maintenance of the hypertensive status. Development of hypertension is supported by the age independent increase of the alpha1A-AR expression in myocardium of ISIAH rats.

1. Flaa A., Eide I.K., Kjeldsen S.E., Rostrup M. Sympathoadrenal stress reactivity is a predictor of future blood pressure: an 18-year follow-up study // Hypertension. 2008. 52. S336–S341.

2. Chattopadhyay N., Kher R., Godbole M. Inexpensive SDS/phenol method for RNA extraction from tissues // Biotechniques. 1993. 15. S24–S26.

3. Fedoseeva L.A., Ryazanova M.A., Antonov E. V. et al. Expression of the renin angiotensin system genes in the kidney and heart of ISIAH hypertensive rats // Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. 2011. 5. (1). S37–S43.

4. Michel M.C., Kanczik R., Khamssi M. et al.   α- And β-adrenoceptors in hypertension: I. Cardiac and renal α₁, β₁, and β₂ adrenoceptors in rat models of acquired hypertension // Cardiovasc. Pharmacol. 1989. 13. S421–S431.

5. Bruckner R., Mugge A., Scholz H. Existence and functional role of alpha1-adrenoceptors in the mammalian heart // J. Mol. Cell. Cardiol. 1985. 17. S639–S645.

6. Lee H.R., Henderson S.A., Reynolds R. et al. α₁-Adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells. Effects on myosin light chain-2 gene expression // Biol. Chem. 1988. 263. S7352–S7358.

7.   Hanna M.K., Khairallah P.A. Alterations of myocardial α₁-adrenergic receptors in hypertensive cardiac hypertrophy in the rat // Arch. Int. Pharmacodyn. Ther. 1986. 283. S80–S93.

8.   Reja V., Goodchild A.K., Pilowsky P.M. Ca­techolamine-related gene expression correlates with blood pressures in SHR // Hypertension. 2002. 40. S342–S347.

9.   Eid H., de Champlain J. Increased inositol monophosphate production in cardiovascular tissues of DOCA-salt hypertensive rats // Hypertension. 1988. 12. S122–S128.

10. Handy D.E., Flordellis C.S., Bogdanova N. N., et al. Diverse tissue expression of rat alpha2-adrenergic receptor genes // Hypertension. 1993. 21. S861–S865.

11. Salomonsson M., Oker M., Kim S. et al. Alpha1-adrenoceptor subtypes on rat afferent arterioles assessed by radio­ligand binding and RT-PCR // Am. J. Physiol. Renal. Physiol. 2001. 281. S172–S178.

12. Blue D.R.Jr., Vimont R.L., Clarke D.E. Evi­dence for anoradrenergic innervation to alpha 1A-adrenoceptors in rat kidney // Br. J. Pharmacol. 1992. 107. S414–S417.

13. Smyth D.D., Umemura S., Pettinger W.A. Re­nal nerve stimulation causes alpha1-adrenoceptor-mediated sodium retention but not alpha2-adreno­ceptor antagonism of vasopressin // Circ. Res. 1985. 57. S304–S311.

14. Intengan H.D., Smyth D.D. Alpha-2a/d adre­no­ceptor subtype stimulation by guanfacine increase osmolar clearance // J. Pharmacol. Exp. Therap. 1997. 281. S48–S53.

15. Saiz J., Lara B., Torres A., Sanchez A. Hyper­tensinogenic factors and renal alpha-adrenoceptors in young SHR and WKY rats // Life Sci. 1987. 41. S2261–S2268.

16. Parini A., Diop L., Ferrari P. et al. Cerebral and renal alpha-adrenoceptors in Milan hypertensive rat strain // Hypertension. 1986. 4. S213–S215.

17. Parini A., Diop L., Dausse J.P., Ben-Ishay D. Sabra rats as a model to differentiate between Na+ and GTP regulation of alph2-adrenoceptor densities // Eur. J. Pharmacol. 1985. 112. S97–S104.

18. McCaughran J.A.Jr., Juno C.J., O’Malley E., Rosenthal M. The ontogeny of renal alpha1- and alpha 2-adrenoceptors in the Dahl rat model of experimental hypertension // J. Auton. Nerv. Syst. 1986. 17. S1–S20.

19. Dawson R.Jr., Oparil S. Renal catecholamines and alpha2-adrenergic receptors in salt-related and genetic hypertension // Pharmacology. 1987. 34. (2–3). S131–S142.

20. Guyenet P.G. The sympathetic control of blood pressure // Nat. Rev. Neurosci. 2006. 7. S335–S346.

Ryazanova M.A. – junior researcher of the laboratory of evolutionary genetics, e-mail: ocean-2006@yandex.ru