Kovalev I V, Baskakov M B, Popov A G, Kilin A A, Minochenko I L, Borodin Iu L, Panov A A, Afinogenova Ia D, Kapilevich L V, Medvedev M A
Department of Biophysics, Department of Normal Physiology, Siberian Medical University, Moskovskii trakt 2, Tomsk, 634050 Russia.
Eksp Klin Farmakol. 2003 Jul-Aug;66(4):25-8.
The results of the membrane potential measurements (by the double sucrose gap junction technique) and the smooth muscle tension determination (by the mechanical force measurements) in the rat aorta showed that vinpocetine potentiates the effect of sodium nitroprusside and nitroglycerin on the smooth muscle cells. In the concentration range of 2-20 microM, vinpocetine produced a dose-dependent inhibition of the Ca2+ conductivity of the membrane and decreased the smooth muscle contractility response. At a concentration of 1 microM, the drug acted as an inhibitor of the phosphodiestherase (PDE) activity and produced the effects similar top those of dibutyryl-cGMP (rather than dibutyryl-cAMP). In the presence of 10 microM of Methylene Blue (an inhibitor of the soluble fraction of guanylate cyclase), the cGMP-dependent effects of vinpocetine were suppressed on the background of 100 microM of sodium nitroprusside, but retained on the background of 10 microM of 3-isobutyl-1-methylxanthine (IBMX), a nonspecific PDE inhibitor. IBMX acted like dibityryl-cGMP and activated the K+ conductivity of the membrane. It is suggested that cGMP-dependent effects of vinpocetine are related to its action upon the Ca2+ and Na+ and (but not K+) conductivity and to the cGMP-induced increase in the contribution of sarcoplasmic calcium to the contractile response.
