[Mechanisms of NO-dependent relaxation in smooth muscles of the rat aorta with nitro compounds]. / Issledovanie mekhanizmov NO-zavisimogo rasslableniia gladkikh myshts aorty krysy s pomoshch'iu nitrosoedinenii.

The membrane potential and smooth muscle tension in rat aorta were studied by the method of sucrose gap junction. It was found that sodium nitroprusside and nitroglycerin produced a dose-dependent membrane repolarization and smooth muscle cell relaxation in rat aorta preliminarily contracted and depolarized by hyperpotassium (40 mM) or phenylephrine solutions. The relaxation effect of sodium nitroprusside was more pronounced on the phenylephrine background. The effect of nitroglycerin showed a different kinetics in time and led to the tolerance development. The effects of both nitro compounds were inhibited by pretreatment with Methylene Blue or potassium channel blockers. It is suggested that nitro vasodilators are involved in the NO-dependent processes in smooth muscle cells of aorta through cGMP-mediated activation of the potassium conductivity and by changing the efficiency of operation of the protein kinase C branch of the Ca2+ signal system.

[Studying cGMP-dependent mechanisms of vinpocetine effect on smooth muscle cells]. / Issledovanie tsGMF-zavisimykh mekhanizmov deistviia vinpotsetina na gladkomyshechnye kletki.

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.

[Myogenic effects of cyclic guanosine monophosphate in smooth muscle cells. Role of protein kinase C]. / Miogennye éffekty tsiklicheskogo guanozinmonofosfata v gladkomyshechnykh kletkakh. Rol' proteinkinazy C.

Heterogeneity of the cGMP-dependent contractility effects of the smooth cells (SMC) was shown in guinea pig ureter by the methods of the double sucrose gap junction. Sodium nitroprusside (SN, 0.1-100 microM) relaxed the high-K+ depolarisationprecontracted SMC but strengthened the SMC constriction triggered by electrical stimulation. In taenia coli, SN or nitroglycerin in the same concentration ranges depressed the electrical or mechanical activity of the SMC and relaxed the SMC, precontracted by depolarization in high-K+ medium. The inhibitor of the phosphodiesterases vinpocetine (1 microM) contributed to the activating effect of SN; the inhibitor of the soluble guanilatcyclase Methilen Blue (10 microM) depressed it. Histamine and mesotone (1-10 microM) increased the action potential and constriction of the SMC triggered by electrical stimulation but decreased the effect of SN. The activator of the protein kinase C (PK-C) phorbol miristoyl-13-acetyl (0.5 microM) changed direction of the SN effects inhibiting both the parameters of an action potential and of the SMC constriction. The pre-treatment with the inhibitor of PK-C calphostin C (0.1 microM) additionally depressed the effects of SN, increasing SMC constriction, especially in the presence of histamine and mesatone. We suggest that c-GMP depressed activity of the PK-C by independent mechanisms operating in SMC.