Augmented EDHF signaling in rat uteroplacental vasculature during late pregnancy.

A successful pregnancy outcome relies on extensive maternal cardiovascular adaptation, including enhanced uteroplacental vasodilator mechanisms. The objective of the present study was to determine the contribution of the endothelium-derived hyperpolarizing factor (EDHF) signaling in pregnancy-enhanced uterine vasodilation, to define the role of Ca(2+)-activated K(+) channels in mediating EDHF effects, and to explore the impact of endothelial Ca(2+) signaling in pregnancy-specific upregulation of EDHF. Fura 2-based measurements of smooth muscle cell (SMC) and endothelial cell cytosolic Ca(2+) concentration ([Ca(2+)](i)) were performed simultaneously with measurements of the diameter of uterine radial arteries from nonpregnant (NP) and late pregnant (LP) rats. Changes in SMC membrane potential of pressurized arteries from LP rats were assessed using glass microelectrodes. After blockade of nitric oxide and prostacyclin production, a cumulative application of ACh induced rapid and effective dilatation of uterine vessels from both NP and LP rats. This vasodilation was associated with SMC hyperpolarization and SMC [Ca(2+)](i) reduction and was abolished by a high-K(+) solution, demonstrating that N(G)-nitro-L-arginine (L-NNA)- and indomethacin-resistant responses are attributable to EDHF. Pregnancy significantly potentiates EDHF-mediated vasodilation in part due to enhanced endothelial Ca(2+) signaling. L-NNA- and indomethacin-resistant responses were insensitive to iberiotoxin but abolished by a combined treatment with apamin and charybdotoxin, supporting the key role of small- and intermediate-conductance K(+) channels in mediating EDHF signaling in the maternal uterine resistance vasculature.

[Effect of adenosine and ATP on electrogenesis and contraction in the smooth muscles of the cerebral arteries]. / Deistvie adenozina i ATF na élektrogenez i sokrashchenie v gladkikh myshtsakh mozgovykh arterii.

The effects of adenosine and ATP on electrogenesis and contraction in smooth muscles of the cattle basilar and middle cerebral arteries was studied with a modified sucrose gap technique. Adenosine (10(-8) - 10(-3) M) and ATP (10(-8) - 10(-6) M) induced relaxation of the muscle strips with no change in resting potential of the muscle cells. ATP (10(-5) - 10(-3) M) led to depolarization of the cell membrane followed by a hyperpolarization which was accompanied by the complex contractile reaction of muscle strips. Adenosine (10(-3) M) caused relaxation comparable to the relaxation induced by Ca++-free solution or by Mn++ ions. This suggests that extracellular Ca++ ions which participate in maintaining of the blood vessel tone enter the smooth muscle cells mainly through the stationary open adenosinesensitive Ca channels of the membrane. Ca++ ions entering the smooth muscle cells through voltage-dependent noninactivating Ca channels contribute to maintaining of cerebral arteries' basal tone. Adenosine does not affect the voltage-dependent influx of extracellular Ca++ ions through the slow noninactivating Ca channels of the cell membrane or through fast inactivating Ca channels, participating in the AP generation.

[The role of calcium and potassium conductance in electrogenesis of smooth-muscle cells of the basilar artery]. / Rol' kal'tsievoi i kalievoi provodimostei v elektrogeneze gladkomyshechnykh kletok osnovnoi arterii.

The role of calcium and potassium conductances in electrogenesis of smooth muscle cells of the bovine basilar artery has been investigated using blocking agents of calcium and potassium channels both in the normal Krebs solution and in hyperpotassium solution under anelectrotonic repolarization of the cell membrane. It is shown that both voltage-operated calcium and potassium conductances participate in generation of gradual action potentials evoked by electrical stimulation. A higher contribution of potassium conductance into the total membrane conductance during depolarization is found to be the main factor interfered with development of full-size action potential.

[Mechanism of the effect of dibasol on the contractile and electric activities of the smooth muscle of the portal vein]. / Issledovanie mekhanizma deistviia dibazola na sokratite'lnuiu i élektricheskuiu aktivnos't gladkoi myshtsy vorotnoi veny.

The effects of dibasol on spontaneous electrical and contractile activities as well as on the reactions evoked by hyperkalemic solution and noradrenaline were studied in smooth muscle of rabbit portal vein. It was shown that dibasol blocked the potential-operated influx Ca2+ into smooth muscle cells. The noninactivating calcium channels were found to be more sensitive to dibasol than inactivating ones. Significant part of the tonic contraction induced by noradrenaline was resistant to dibasol suggesting its weak effect on Ca2+ influx through calcium channels operated by alpha 1-adrenoceptors. It is supposed that vasodilative effect of dibasol is associated with blocking the influx Ca2+ through potential-operated noninactivating calcium channels into smooth muscle cells.

[Excitation-contraction coupling in the smooth muscle of the femoral artery under the effects of noradrenaline]. / Sopriazhenie vozbuzhdeniia-sokrashcheniia v gladkoi myshtse bedrennoi arterii pri deistvii noradrenalina.

Noradrenaline (5 x 10(-8) - 10(-5) M) induced a dose-dependent contraction of muscle strips from rabbit femoral artery. At concentrations higher than 10(-7) M noradrenaline evoked also a depolarization of smooth muscle cells due to an increase in sodium and/or chloride permeability of the membrane. Repolarization of the membrane to original level by inwardly applied current resulted in restoration of membrane resistance and partial relaxation of noradrenaline-evoked contraction. The same part of contraction was also blocked by verapamil. In calcium-free EGTA-containing solution noradrenaline induced only a small transient contraction. These findings indicate that noradrenaline-activated sodium (or chloride) permeability is voltage dependent. Noradrenaline evoked contraction is activated by calcium ions entered the cell through receptor-operated and partly through voltage-operated calcium channels.

Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries.

The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1-100 microM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K(+) solution. K(+)-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co(2+) (100-200 microM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K(+)-induced contraction. In the presence of Co(2+) and in low-Na(+) solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca(2+) influx through voltage-dependent Ca(2+) channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca(2+) channels and Ca(2+) sensitization of the contractile process.

Role of intracellular Ca(2+) release in histamine-induced depolarization in rabbit middle cerebral artery.

The role of Ca(2+) mobilization from intracellular stores and Ca(2+)-activated Cl(-) channels in caffeine- and histamine-induced depolarization and contraction of the rabbit middle cerebral artery has been studied by recording membrane potential and isometric force. Caffeine induced a transient contraction and a transient followed by sustained depolarization. The transient depolarization was abolished by ryanodine, DIDS, and niflumic acid, suggesting involvement of Ca(2+)-activated Cl(-) channels. Histamine-evoked transient contraction in Ca(2+)-free solution was abolished by ryanodine or by caffeine-induced depletion of Ca(2+) stores. Ryanodine slowed the development of depolarization induced by histamine in Ca(2+)-containing solution but did not affect its magnitude. In arteries treated with 1 mM Co(2+), histamine elicited a transient depolarization and contraction, which was abolished by ryanodine. DIDS and niflumic acid reduced histamine-evoked depolarization and contraction. Histamine caused a sustained depolarization and contraction in low-Cl(-) solution. These results suggest that Ca(2+) mobilization from ryanodine-sensitive stores is involved in histamine-induced initial, but not sustained, depolarization and contraction. Ca(2+)-activated Cl(-) channels contribute mainly to histamine-induced initial depolarization and less importantly to sustained depolarization, which is most likely dependent on activation of nonselective cation channels.

[Effect of ATP and adenosine on the spontaneous electrical and contractile activity of portal vein smooth muscle cells]. / Vliianie ATF i adenozina na spontannuiu élektricheskuiu i sokratitel'nuiu aktivnost' gladkomyshechnykh kletok vorotnoi veny.

It was shown in experiments on smooth muscle cells of the guinea-pig, rat and rabbit portal vein that adenosine (AD) and ATP exert both excitatory and inhibitory effects. The former effect is manifested by depolarization of the cell membrane, an increase in the frequency of action potentials (AP) and phasic contractions, as well as by the appearance of tonic contractions. The latter effect is accompanied by the inhibition of spontaneous activity and relaxation of a smooth muscle strip. It is suggested that the effects of ATP and AD are mediated by specific inhibitory and excitatory chemoreceptors in the muscle cell membrane, the former receptors being related to potential-dependent ionic channels, while the latter ones to potential-independent chemosensitive ionic channels. Apamine, a powerful blocker of non-adrenergic inhibition in the gastrointestinal tract, produces no influence on ATP and AD effects induced in smooth muscle cells of the portal vein.

Temperature and protein kinase C modulate myofilament Ca2+ sensitivity in pressurized rat cerebral arteries.

The effects of pharmacological activation and inhibition of protein kinase C (PKC) and temperature on the relationship between cytoplasmic Ca2+ and lumen diameter were studied in pressurized (50 mmHg) rat posterior cerebral arteries permeabilized with alpha-toxin. Increasing Ca2+ concentrations (30 nM-10 microM, 22 degrees C) induced stable, concentration-dependent constrictions with a half-maximal effective concentration (EC50) of 112 nM. The maximal constriction was 80% of baseline diameter and 157% of that during depolarization of nonpermeabilized vessels with 124 mM KCl. Elevation of temperature to 37 degrees C increased the EC50 to 246 nM and enhanced the steepness of concentration-response curves. Exposure of permeabilized arteries to indolactam V, an activator of PKC, resulted in a significant myofilament Ca2+ sensitization (e.g., EC50 at 5 microM = 126 nM) without changing efficacy. The effects of calphostin C, a PKC inhibitor, on Ca2+ sensitivity were minimal; however, the amplitude of Ca2+-induced constrictions in both control and indolactam-treated arteries was suppressed in a concentration-dependent manner. Thus 1) temperature is an important variable in studies of arterial Ca2+ sensitivity, and 2) changes in PKC activity can significantly alter both myofilament sensitivity to and constrictor efficacy of cytosolic Ca2+.

[Mechanism of action of voltaren on the smooth muscles of the blood vessels]. / Mekhanizm deistviia vol'tarena na gladkie myshtsy krovenosnykh sosudov.

The effect of voltaren on the electrical and contractile activity of smooth muscle cells of the rabbit portal vein and the bovine cerebral arteries was studied by sucrose gap method. Voltaren was found to rarefy (10(-6)-10-10(-3)mol/l) or to suppress (10(-4)-10(-3)mol/l) spontaneous electrical and contractile activity and to relax the portal vein muscle strips. At concentrations of 5.10(-6)-5.10(-3) mol/l voltaren caused a dose-dependent relaxation of the cerebral arterial muscle strips. The relaxation of the smooth muscles of the blood vessels induced by voltaren is suggested to be due to inhibition of calcium ions influx into muscle cells through different types of calcium channels.

[Electrophysiological analysis of the action of kavinton on the smooth muscles]. / Elektrofiziologicheskii analiz deistviia kavintona na gladkie myshtsy.

Cavinton at a concentration of 10(-7)-10(-5) M was found to have a dose-dependent relaxing effect on bovine cerebral artery smooth muscles, without changing the resting potential and membrane resistance. Smooth muscles of the rabbit portal vein and guinea-pig taenia coli were insensitive to low cavinton concentrations. The results are consistent with the hypothesis that relaxing action of cavinton is due to the blocking of Ca2+ ions influx into the cells of cerebral artery through receptor-operated calcium channels. At higher concentrations (exceeding 10(-5) M) cavinton exerts nonspecific influence on the smooth muscles under study, inhibiting their excitability and decreasing membrane resistance resulting in the attenuation of tetanic contractions in the smooth muscles of the portal vein and taenia coli.

[The role of intra- and extracellular Ca in the activation of contraction of pulmonary artery smooth muscles induced by serotonin]. / Rol' vnutri- i vnekletochnogo Ca v aktivatsii sokrashcheniia gladkikh myshts legochnoi arterii, vyzyvaemogo serotoninom.

In Ca-free EGTA-containing solution serotonin induced a transient contraction of rabbit pulmonary artery smooth muscle which decayed to nearly steady-state level accounted for 17.7 +/- 1.6% of original contraction in Krebs solution. Both phasic and tonic components of this contraction were effectively inhibited by verapamil and Cd2+. Caffeine induced no contraction of muscle strips if it was applied after withdrawal of serotonin. But when the sequence of these drugs application was reversed, serotonin still evoked contraction with reduced phasic component. The results obtained in these experiments suggest, that serotonin-induced contraction of pulmonary artery smooth muscle is partly (less than 20%) due to mobilization of bound calcium from at least two stores located on the opposite sides of the cell membrane. Calcium released from external store site enters the cell via receptor-operated calcium channels.