Biomedical subjects

Menshikov MYu

Publications and source records attributed to Menshikov MYu.

4 recordsLinked to original sources

PubMed1993

Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

Adenosine Diphosphate↗

PubMed1988

Platelets as a model for studying the action of antihypertensive drugs.

The action of different antihypertensive drugs on Ca2+ concentration in human platelets was studied under in vitro conditions and during the treatment of hypertensive persons. Several calcium antagonists (verapamil, nifedipine, and nicardipine) acted to block an increase of Ca2+ concentration in platelets which was induced by platelet activating factor (PAF), adenosine diphosphate, and U46619, the stable analog of thromboxane A2. All calcium antagonists suppressed dose-dependent calcium responses induced by each agonist. In a group of stable hypertensive patients, the basal Ca+ level in platelets was significantly higher than the level in mildly hypertensive or normotensive individuals. The induced increase in Ca2+ in the platelets of stable hypertensive patients was also higher, but this difference was not significant. Treatment of hypertensive patients with nifedipine for 3 weeks led to a decrease in calcium responses induced by all activators, but this decrease was significant only when PAF was used for platelet stimulation. Nifedipine added to platelets induced a nearly identical decrease in PAF-dependent calcium responses before and after therapy. Treatment with nifedipine in combination with furosemide and propranolol led to a more significant decrease in calcium responses than that expressed with monotherapy. In vitro experiments showed that furosemide has a calcium-blocking action on platelets, but that it is less expressed than the action of calcium antagonists. Low doses of propranolol did not influence calcium platelet responses, but high doses potentiated them slightly. A significant correlation was found between the percentage change in mean arterial pressure and in the PAF-induced responses with either monotherapy or combination drug therapy. Measurement of calcium responses before and after intravenous infusion of prostaglandin E2 showed that this procedure leads to a decrease in calcium responses that lasts for several days. The data suggest that platelets may be used as a model for investigating the action of drugs that influence calcium exchange when these drugs are administered chronically.

Adult↗

PubMed1988

The hypertensive heart: pathogenesis, variants, and prognostic value.

We examine the heart's involvement in arterial hypertension, reporting on several studies of hypertensive patients showing that left ventricular myocardial mass is a significant prognostic indicator of essential hypertension and that left ventricular hypertrophy (LVH) correlates with an induced increase in Ca2+ concentration in platelets. We also consider the LVH variant of asymmetric hypertrophy and the role of the hypertensive heart in coronary insufficiency, and we speculate on the significance of the degree of LVH and asymmetric hypertrophy as risk factors for predicting cardiac complications of essential hypertension.

Blood Platelets↗

PubMed1984

Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidil.

Trapidil (N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine ) inhibits platelet spreading and aggregation induced by arachidonic acid (AA), a stable analogue of prostaglandin (PG) endoperoxides (U46619), ADP, and low concentrations of thrombin, but not by A23187 and high concentrations of thrombin. Trapidil does not affect platelet adenylate cyclase but inhibits the cAMP PDE by approx. 50%. PDE inhibition proceeds via a competitive mechanism (Ki = 0.52 mM) and is not mediated by calmodulin inhibition. Trapidil does not change the platelet basal cAMP level but potentiates an increase of cAMP induced by the stable prostacyclin analogue (6 beta-PGI1). These results suggest that trapidil antiplatelet effects may be due to the inhibition of platelet PDE.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗