Aim: The effects of diterpene alkaloid zongorin and 1–O– benzoylnapellin on contractile activity of rat aorta smooth muscle were investigated. Material and methods: Contractile activity of rat aortic smooth muscle, precontracted with high KCl and phenylephrine, was evaluated by mechanographic technique using isometric force transducer FT–03(Grass–Telefactor, USA). Results: Both alkaloids in dose–dependent manner inhibited aortic rings contraction induced by 50 mMKCl. These effects of zongorin and 1–O–benzoylnapellinwere significantly reduced in the absence of extracellular Ca2+ or in the presence of verapamil, which more potently inhibited the effect of zongorin. In contrast to zongorin 1–O–benzoylnapellin also potently inhibited the contraction induced by 1 µM phenylephrine. Conclusions: Alkaloids zongorin and 1–O–benzoylnapellin possesses potent relaxant effect which is related to inhibition of Ca2+ transport through multiple Ca2+pathways, including voltage–dependent and receptor–operated Ca2+–channels, as well as, Ca2+ release from sarcoplasmic reticulum. The differences in the mechanism of relaxant action of alkaloids possible are due to the presence of the benzoyloxy group in the structure of 1–O–benzoylnapellin, which by increasing its lipophilicity can facilitate its penetration into smooth muscle cells and thus modify the Ca2+ transport at the level of sarcoplasmic reticulum.
1. Brozovich F.V., Nicholson C.J., Degen C.V. et al. Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders // Pharmacol. Rev. – 2016. – Vol. 68. – P. 476-532. 2. Harrison D.G., Gongora M.C. Oxidative stress and hypertension // Med. Clin. North Amer. – 2009. – Vol. 93. – P. 621-635. 3. Havranek E.P. et al. Social Determinants of Risk and Outcomes for Cardiovascular Disease: A Scientific Statement From the American Heart Association // Circulation. – 2015. – Vol. 132. – P. 873-898. 4. Lifton R.P., Gharavi A.G., Geller D.S. Molecular mechanisms of human hypertension // Cell. – 2001. – Vol. 104. – P. 545-556. 5. Mozaffarian D., Benjamin E.J., Go A.S. et al. Heart disease and stroke statistics – 2015 update: a report from the American Heart Association // Circulation. – 2015. – Vol. 131. – P. 29-322. 6. Shi C.C., Liao J.F., Chen C.F. Comparative study on the vasorelaxant еffects of Harmala Alkaloids // Jpn. J. Pharmacol. – 2012. – Vol. 85. – P. 299-305. 7. Tan B., Zhang C. Pharmacological mechanisms of cardiovascular actions of diterpenoids of Andrographis paniculata // Presented at INABIS '98. – 5th World Congress on Biomedical Sciences at McMaster University, Canada. – 1998. 8. Wang G.J., Shan J., Pang P.T., Chen C.F. The vasorelaxing action of rutacarpine // J. Pharmacol. Exp. Ther. – 1999. – Vol. 276. – P. 1016-1021. 9. Zambon A., Arfе A., Corrao G., Zanchetti A. Relationships of different types of event to cardiovascular death in trials of antihypertensive treatment: an aid to definition of total cardiovascular disease risk in hypertension // J. Hypertens. – 2014. – Vol. 32. – P. 495-504. 10. Zamponi G.W., Striessnig J., Koschak A., Dolphin A.C. The physiology, pathology, and pharmacology of voltage–gated calcium channels and their future therapeutic potential // Pharmacol. Rev. – 2015. – Vol. 67. – P. 821-870.
"EFFECTS OF DITERPENE ALKALOIDS ZONGORIN AND 1–O–BENZOYLNAPELLIN ONСОNTRACTILE ACTIVITY OF RAT AORTA SMOOTH MUSCLE,"
Central Asian Journal of Medicine: Vol. 2019
, Article 5.
Available at: https://uzjournals.edu.uz/tma/vol2019/iss1/5