arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2009-15-6-683-687arthyper-1453Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМеханизмы формирования кальций-зависимой гипертензии на модели кардиомиоцитов крыс в культуреThe mechanisms of Ca2+-dependent hypertension formation on the model of rat cardiomyocytes in the cultureЗахаровЕ. А.ZakharovE. A.noemail@neicon.ruКлюеваН. З.KlyuevaN. Z.noemail@neicon.ruБелостоцкаяГ. Б.BelostotskayaG. B.noemail@neicon.ruИнститут эволюционной физиологии и биохимии им. И.М.Сеченова РАНРоссияSechenov Institute of Evolutionary Physiology and Biochemistry of RASRussian FederationИнститут физиологии им. И.П.Павлова РАНРоссияPavlov Institute of Physiology of RASRussian Federation200928122009156683687Copyright © Захаров Е.А., Клюева Н.З., Белостоцкая Г.Б., 20092009Захаров Е.А., Клюева Н.З., Белостоцкая Г.Б.Zakharov E.A., Klyueva N.Z., Belostotskaya G.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1453

Цель исследования - изучение физиологической активности рианодиновых (РиР) и дигидропиридиновых (ДГПР) рецепторов в кардиомиоцитах спонтанно гипертензивных (SHR) и нормотензивных (WKY, Wistar) крыс от рождения до 6-недельного возраста. Материалы и методы. Активность рецепторов оценивали по скорости нарастания внутриклеточной концентрации Ca2+ ([Ca2+]i) в культивируемых (5 дней) кардиомиоцитах: в ответ на действие 4-хлор-м-крезола (4-ХмК) для РиР и Bay K8644 (BayK) - для ДГПР. Результаты. После трехнедельного возраста в миоцитах крыс SHR регистрировалось резкое увеличение скорости нарастания [Ca2+]i (2,9 ± 0,8 раза) в ответ на действие 4-ХмК (2мМ) по сравнению со снижением скорости высвобождения Ca2+ через РиР у крыс Wistar и WKY. BayK (80 μM) также индуцировал более резкое нарастание [Ca2+]i в кардиомиоцитах крыс SHR (3,4 ± 0,3 раза) по сравнению с крысами линий Wistar (2,3 ± 0,2 раза) и WKY (1,2 ± 0,1 раза) того же возраста. Выводы. В кардиомиоцитах крыс SHR и WKY, в отличие от нормотензивных крыс Wistar, наблюдается постепенный рост активности ДГПР, который идет параллельно формированию Ca2+-зависимого выброса Ca2+ (CICR) (3 недели) и резкое возрастание активности РиР в миоцитах крыс SHR в конце предгипертензионного периода (6 недель).

Objective. To study the ryanodine (RyR) and dihydropyridine (DHPR) receptor physiological activity in cardiomyocytes of spontaneously hypertensive (SHR) and normotensive (WKY, Wistar) rats aged 0-6 weeks. Design and methods. The receptor activity was estimated by the elevation rate of intracellular Ca2+ concentration ([Ca2+]i) in the cardiomyocyte culture (5 days): in response to 4-chloro-m-cresol (4-CmC) action for RyRs and to Bay K8644 (BayK) one - for DHPR. Results. In response to 4-CmC (2 mM), a drastic increase in the rate of [Ca2+]i accumulation (2,9 ± 0,8 times) was registered in SHR myocytes cultivated for 3 and more weeks versus a decrease in the rates of Ca2+ release via the RyRs of Wistar and WKY rat cardiomyocytes. BayK (80 μM) also induced more sharp [Ca2+]i elevation in SHR cardiomyocytes (3,4 ± 0,3-fold increase) as compared to age-matched Wistar (2,3 ± 0,2-fold increase) and WKY (1,2 ± 0,1-fold increase) ones. Conclusion. In SHR and WKY cardiomyocytes, as compared to normotensive Wistar rats, gradual growth of DHPR activity is observed, which follows by Ca2+-induced Ca2+ release (CICR) (3 weeks) and drastic activation of RyR in SHR myocytes at the end of prehypertensive period (6 weeks).

рианодиновые рецепторыдигидропиридиновые рецепторыспонтанно гипертензивные крысы[Ca2+]iCa2+-зависимый выброс кальцияReferencesZwadlo C., Borlak J. Disease-associated changes in the expression of ion channels, ion receptors, ion exchangers and Ca2+-handling proteins in heart hypertrophy // Toxicol. Appl. Pharmacol. - 2005. - Vol. 207. - P. 244-256.Zwadlo C., Borlak J. Disease-associated changes in the expression of ion channels, ion receptors, ion exchangers and Ca2+-handling proteins in heart hypertrophy // Toxicol. Appl. Pharmacol. - 2005. - Vol. 207. - P. 244-256.Чурина С.К., Клюева Н.З., Кузнецов С.Р. и др. К патогенезу артериальной гипертензии при дефиците кальция в питьевой воде // Артериальная гипертензия. - 1995. - Т. 1, № Х. - С. 25-30.Чурина С.К., Клюева Н.З., Кузнецов С.Р. и др. К патогенезу артериальной гипертензии при дефиците кальция в питьевой воде // Артериальная гипертензия. - 1995. - Т. 1, № Х. - С. 25-30.Kawaguchi H., Sano H., Iizuka K. et al. Phosphatidylinositol metabolism in hypertrophic rat heart // Circ. Res. - 1993. - Vol. 72, № 5. - P. 966-972.Kawaguchi H., Sano H., Iizuka K. et al. Phosphatidylinositol metabolism in hypertrophic rat heart // Circ. Res. - 1993. - Vol. 72, № 5. - P. 966-972.Zwadlo C. and Borlak J. Nifedipine represses ion channels, transporters and Ca2+-binding proteins in hearts of spontaneously hypertensive rats // Toxicol. Appl. Pharmacol. - 2006. - Vol. 213. - P. 224-234.Zwadlo C. and Borlak J. Nifedipine represses ion channels, transporters and Ca2+-binding proteins in hearts of spontaneously hypertensive rats // Toxicol. Appl. Pharmacol. - 2006. - Vol. 213. - P. 224-234.Shorofsky S.R., Aggarwal R., Corretti M. et al. Cellular mechanisms of altered contractility in the hypertrophied heart. Big hearts, big sparks // Circ. Res. - 1999. - Vol. 84. - P. 424-434.Shorofsky S.R., Aggarwal R., Corretti M. et al. Cellular mechanisms of altered contractility in the hypertrophied heart. Big hearts, big sparks // Circ. Res. - 1999. - Vol. 84. - P. 424-434.Escobar A.L., Ribeiro-Costa R., Villalba-Galea C. et al. Developmental changes of intracellular Ca2+-transients in beating rat hearts // Am. J. Physiol. Heart Circ. Physiol. - 2004. - Vol. 286. - P. H971-H978.Escobar A.L., Ribeiro-Costa R., Villalba-Galea C. et al. Developmental changes of intracellular Ca2+-transients in beating rat hearts // Am. J. Physiol. Heart Circ. Physiol. - 2004. - Vol. 286. - P. H971-H978.Perez C.G., Copello J.A., Li Y. et al. Ryanodine receptor function in newborn rat heart // Am. J. Physiol. Heart Circ. Physiol. - 2005. - Vol. 288. - P. H2527-H2540.Perez C.G., Copello J.A., Li Y. et al. Ryanodine receptor function in newborn rat heart // Am. J. Physiol. Heart Circ. Physiol. - 2005. - Vol. 288. - P. H2527-H2540.Bers D.M. Excitation-contraction coupling and cardiac contractile force. - 2d ed. - Dordrecht, Boston, London: Kluwer Academic, 2001. - 427 p.Bers D.M. Excitation-contraction coupling and cardiac contractile force. - 2d ed. - Dordrecht, Boston, London: Kluwer Academic, 2001. - 427 p.Grynkiewicz G., Роenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties // J. Biol. Chem. - 1985. - Vol. 260. - P. 3440-3450.Grynkiewicz G., Роenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties // J. Biol. Chem. - 1985. - Vol. 260. - P. 3440-3450.Bukoski R.D. Intracellular Ca2+ metabolism of isolated resistance arteries and cultured vascular myocytes of spontaneously hypertensive and Wistar- Kyoto normotensive rats // J. Hypertens. - 1990. - Vol. 8, № 1. - P. 37-43.Bukoski R.D. Intracellular Ca2+ metabolism of isolated resistance arteries and cultured vascular myocytes of spontaneously hypertensive and Wistar- Kyoto normotensive rats // J. Hypertens. - 1990. - Vol. 8, № 1. - P. 37-43.Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Abnormal calcium handling in vascular smooth muscle cells of spontaneously hypertensive rats // J. Hypertens. - 1990. - Vol. 8, № 4. - P. 369-375.Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Abnormal calcium handling in vascular smooth muscle cells of spontaneously hypertensive rats // J. Hypertens. - 1990. - Vol. 8, № 4. - P. 369-375.Bukoski R.D., Lastelic B.A., Xue H. et al. Intracellular Ca2+ and force generation determined in resistance arteries of normotensive and hypertensive rats // J. Hypertens. - 1994. - Vol. 12, № 1. - P. 15-21.Bukoski R.D., Lastelic B.A., Xue H. et al. Intracellular Ca2+ and force generation determined in resistance arteries of normotensive and hypertensive rats // J. Hypertens. - 1994. - Vol. 12, № 1. - P. 15-21.Katoh H., Schlotthauer K., Bers D.M. Transmission of information from cardiac dihydropyridine receptor to ryanodine receptor: evidence from BayK 8644 effects on resting Ca(2+) sparks // Circ. Res. - 2000. - Vol. 87, № 2. - P. 106-111.Katoh H., Schlotthauer K., Bers D.M. Transmission of information from cardiac dihydropyridine receptor to ryanodine receptor: evidence from BayK 8644 effects on resting Ca(2+) sparks // Circ. Res. - 2000. - Vol. 87, № 2. - P. 106-111.Asano M., Matsuda T., Hayakawa M. et al. Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats // Eur. J. Pharmacol. - 1993. - Vol. 247, № 3. - P. 295-304.Asano M., Matsuda T., Hayakawa M. et al. Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats // Eur. J. Pharmacol. - 1993. - Vol. 247, № 3. - P. 295-304.Kubo T., Taguchi K., Ueda M. L-type calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats: effects of calcium agonist and antagonist // Hypertens. Res. - 1998. - Vol. 21, № 1. - P. 33-37.Kubo T., Taguchi K., Ueda M. L-type calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats: effects of calcium agonist and antagonist // Hypertens. Res. - 1998. - Vol. 21, № 1. - P. 33-37.

The authors declare that there are no conflicts of interest present.