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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2003; 49(3): 118-125

High altitude hypoxiaincreases vasodilative reaction on nytroglicerin in healthy subjects

S.A.Bekuzarova, A.S.Khromov, L.B.Doloman, I.A.Beslaneev, H.A.Kurdanov

    International Center of Astronomical and MedicoecologicalInvestigations, Terskol, Russia; Institute of Pharmacologyand Toxicology, Kiev; A. A. Bogomoletz Institute of Physiolo-gy, Kiev, Ukraine


Abstract

After more than centenary successful use of nitroglycerin in clinical practice, scientists revealed that its medicinal effect is based on release of potent vasodilator nitric oxide (NO). More-over, the experiments showed that NO plays an important role in hypoxia vasodilator mechanisms. Since nitroglycerin is an exogenous NO donor and moderate hypoxia facilitates release of endogenous NO, we suggested that nitroglycerin effects are changed in high altitude. To examine this suggestion, we have carried out a standard nitroglycerin test for healthy volunteers living in high and low altitude areas. Comparison of obtained results showed that the use of oral nitroglycerin in high altitude areas is accompanied with significant prolonged decrease in blood pressure and total vascular resistance. So, we first found that high altitude hypoxia strengthens and extends nitroglycerin-induced peripheral vasodilation in healthy subjects. This effect might be caused by additive vasodilator effect of nitroglycerin and moderate hypoxia. This data should be taken into account when prescribing exogenous and endogenous NO donors to treat patients in high altitude areas.

Full text: (PDF, in Ukrainian)

References

  1. Алиев М.А. Гипертония и горный климат. – Фрунзе: Илим, 1966. – 315 с.
  2. Доломан Л.Б., Сагач В.Ф., Курданов Х.А. та ін. Особливості кардіогемодинаміки та ендотелійзалежної судинної реактивності у мешканців високогір’я // Фізіол. журн. – 2002. – 48, №4. – С. 33- – 8.
  3. Молдоташев И.К. Особенности фармакотерапии хронической сердечной недостаточности в условиях высокогорья// Терап.архив. – 1988. – 60, №2. – С.92 – 96.
  4. Моссе І.В., Тишкін С.М., Соловйов А.І. Порівняльна характеристика ефективності дії NO-донорів на коронарні артерії свині в нормі та при гипоксії // Ліки. – 1998. – №5. – С.9 – 12.
  5. Реутов В.П., Сорокина Е.Г., Охотин В.Е., Косицын Н.С. Циклические превращения оксида азота в организме млекопитающих. – М.: Наука, 1998. – 159 с.
  6. Сагач В.Ф., Доломан Л.Б., Коцюруба А.В. та ін. Збільшений вміст стабільних метаболітів оксиду азоту в крові мешканців високогір’я // Фізіол. журн. – 2002. – 48, №5. – С. 3 – 8.
  7. Соловьев А.И. цАМФ-зависимый механизм расслабления сосудистых гладкомышечных клеток при гипоксии, не связанный со снижением концентрации Са2+ в миоплазме // Докл. АН СССР. – 1985. – 285, №5. – С. 1252 – 1256.
  8. Соловьев А.И., Стефанов А.В. Механизмы изменения кальциевой проводимости сарколеммы гладкомышечных клеток сосудов при гипоксии // Физиол. журн. СССР. – 1985. – 71, №12. – С. 1560 – 1567.
  9. 9. Arnold W.P., Mittal C.K., Katsuki S., Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations// Proc. Natl. Acad. Sci. USA. – 1977. – 74, N8. – 3203 – 3207.
  10. 10. Chen Z., Zhang J., Stamler J.S. Identification of the enzymatic mechanism of nitroglycerin bioactivation // Ibid. – 2002. – 99. – Р. 8306 – 8311.
  11. Earley S., Naik J.S., Walker B.R. 48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization// Amer. J. Physiol. Regul. Integr. Comp. Physiol. – 2002. – 283, № 1. – P. R79 – 85.
  12. Faller D.V. Endothelial cell responses to hypoxic stress// Clin. Exp. Pharmacol. Physiol. – 1999. – 26, № 1. – P. 74 – 84.
  13. Franco-Obregon A., Lopez-Barneo J. Low pO2 inhibits calcium channel activity in arterial smooth muscle cells // Amer. J. Physiol. – 1996. – 271, №6. – P. H2290 – H2299.
  14. Franco-Obregon A., Urena J., Lopez-Barneo J. Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation // Proc. Nat. Acad. Sci. USA – 1995. – 92, №10. – P. 4715 – 4719.
  15. Fukuda S., Sakuma K., Tsukui A. et al. Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and hydralazine on isolated porcine coronary arteries // J. Cardiovasc Pharmacol. – 1994. – 23, N5. – P. 852 – 858.
  16. Giordano E., Guarnieri C., Muscari C., Caldarera C.M. Molecular mechanisms of response to low oxygen tension in the vascular wall // Cardiologia. – 1999. – 44, № 9. – P.779 – 782.
  17. Ignarro L. J. Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein// Circulat. Res. – 1989. – 65, № 1. – P. 1 – 21.
  18. Ignarro L. J., Lippton H., Edwards J.C. et al. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates // J. Pharmacol. Exp. Ther. – 1981. – 218. – P. 739 – 749.
  19. 19. Ignarro L.J., Ross G., Tillisch J. Pharmacology of endothelium-derived nitric oxide and nitrovasodilators // J Med. – 1991. – 154, № 1. – P. 51 – 62.
  20. 20. Ishimura N., Kitaguchi K., Tatsumi K., Furuya H. Nitric oxide involvement in hypoxic dilatation of pial arteries in the cat// Anesthesiology. – 1996. – 85, N6. – P.1350 – 1356.
  21. Kostyuk P.G., Stanika R.L., Koval L.M., Lukyanetz E.A. Intracellular mechanisms of hypoxia-induced changes in calcium homeostasis in neurons. – In: International conference «Astroeko-2002», Terskol, Russia (12 – 16 аugust, 2002) – Terskol, 2002. – P.53.
  22. Mc Danniel N., Chen X-L., Singer H. et al. Nitrovasodilatators relax arterial smooth muscle by decreasing {Ca 2+]I and uncoupling stress from myosin phosphorylation/ / Amer. J. Physiol. – 1992. – 263. – P. C.461 – C.46.
  23. Murad F., Mittal C.K., Arnold W.P. et al. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin// Adv. Cyclic Nucleotide Res. – 1978. – 9. – P. 145 – 158.
  24. Parker J.O., Parker J.D., Caldwell R.W. et al. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy // J.Amer. Coll. Cardiol. – 2002. – 39, №7. – P. 1199 – 1203.
  25. Rafflenbeul W., Bassenge E., Lichtlen P. Konkurrenz zwischen endothelabhangiger und Nitroglygerin-induzierter koronarer Vasodilatation// Z. Kardiol. – 1989. – 78, Suppl. 2. – P. 45 – 47.
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