350 rub
Journal №4 for 2011 г.
Article in number:
Effects of endothelin on reactivity of pulmonary and renal arteries under chronic endothelin converting enzyme blockade in rats
Authors:
S.I. Sofronova, M.E. Ilatovskaya, O.S. Tarasova, V.F. Pozdnev, N.A. Medvedeva
Abstract:
Endothelin (ET-1) is produced in the vascular endothelium under endothelin converting enzyme (ECE) action. In overphysiological concentration ET-1 has an evident vasoconstrictor activity but the ET-1 role in circulation control in health is poorly known. In this work we investigated the changes of rat pulmonary and renal arteries reactivity after endothelin converting enzyme inhibition by substance PP-36 (consumption with drinking water in dosage of 1.8 mg/kg per day during two weeks). PP-36 consumption had no influence on systemic arterial pressure. PA constriction in response to α1-adrenoreceptor agonist phenylephrine didn-t change while RA sensitivity to phenylephrine significantly increased. PA endothelium-independent relaxation (to sodium nitroprusside) didn-t change but endothelium-dependent relaxation (to acetylcholine) significantly increased which can be due to increase in nitric oxide production by the endothelium. RA responses to both sodium nitroprusside and acetylcholine increased which can be due to alteration of endothelial secretion and/or higher smooth muscle sensitivity to NO. Therefore ECE inhibition may be accompanied by enhancement of arterial constriction as well as relaxation. Probably in health ET-1 action contributes to vessel resistance stabilization.
Pages: 29-34
References
  1. Ашмаpин И. П., Коpолева С.В. Закономеpности взаимодействия и функциональный континуум нейpопептидов (на пути к единой концепции) // Вестник Росс. акад. мед. наук. 2002. № 6. С. 40 - 48.
  2. Khimji A.K., D. Rockey C. Endothelin - biology and disease. Cell. Signal. 2010. 22(11). Р. 1615 - 1625.
  3. Turner A.J., Murphy L.J. Molecular pharmacology of endothelin converting enzymes // Biochem. Pharmacol. 1996. 51(2). Р. 91-102.
  4. Makita T., Sucov H.M., Gariepy C.E., Yanagisawa M., Ginty D.D. Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons // Nature. 2008. 452(7188). Р. 759 - 763.
  5. Dhaun N., Goddard J., Kohan D.E., Pollock D.M., Schiffrin E.L., Webb D.J. Role of endothelin-1 in clinical hypertension: 20 years on // Hypertension. 2008. 52(3). Р. 452 - 459.
  6. Kalani M. The importance of endothelin-1 for microvascular dysfunction in diabetes // Vasc. Health Risk Manag. 2008. 4(5). Р. 1061 - 1068.
  7. Симонова А.И., Позднев В.Ф., Гомазков О.А., Медведева Н.А. Хроническое применение ингибитора эндотелин-превращающего фермента снижает степень развития гипоксической формы легочной гипертензии у крыс // Росс. физиол. ж. имени И.М. Сеченова. 2008. 94(7). Р. 777 - 784.
  8. Kirkby N.S., Hadoke P.W., Bagnall A.J., Webb D. J. The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house - // Br. J. Pharmacol. 2008. 153(6). Р. 11051119.
  9. Opitz C.F., R. Ewert., W. Kirch, D. Pittrow, Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter - // Eur Heart J. 2008. 29(16). Р. 1936 - 1948.
  10. Dai Z. K., Hsieh C.C., Chai C.Y., Wu J.R., Jeng A.Y., Chou S.H., Wu B.N., Yeh J.L., Chen I.J., Tan M.S. Protective effects of a dual endothelin converting enzyme/neutral endopeptidase inhibitor on the development of pulmonary hypertension secondary to cardiac dysfunction in the rat // Pediatr. Pulmonol. 2010. 45(11). Р. 1076 - 1085.
  11. Позднев В.Ф., Гомазков О.А., Давыдова М.П., Медведева Н.А. Синтез и гемодинамические эффекты нового ингибитора эндотелин-превращающего фермента // Бюлл. эксперим. биол. и мед. 1998. 126(11). Р. 26 - 29.
  12. Rufanova V.A., Pozdnev V.F., Kalenikova E.I., Postnikov A.B., Storozhilova A.N., Masenko V.P., Gomazkov O.A., Medvedev O.S., Medvedeva N.A. Endothelin-converting enzyme inhibition in the rat model of acute heart failure: heart function and neurohormonal activation // Exp. Biol. Med. (Maywood). 2009. 234(10). Р. 1201 - 1211.
  13. Nakano D., Pollock J.S., Pollock D.M. Renal medullary ETB receptors produce diuresis and natriuresis via NOS1 // Am. J. Physiol. 2008. 294. F1205-F1211.
  14. Dupuis J., Goresky C.A., Fournier A. Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors // J. Appl. Physiol. 1996. 81(4). Р. 1510 - 1515.
  15. Damon D.H. Endothelin and post-ganglionic sympathetic neurons // Clin. Expl. Pharmacol. Physiol. 1999. 26. Р. 1000 - 1003.
  16. Тарасова О.С., Пуздрова В.А., Каленчук В.У., Кошелев В.Б. Повышение чувствительности гладкой мышцы сосудов к констрикторным влияниям после денервации и при снижении давления крови // Биофизика. 2006. 51(5).