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Biomedical subjects

J V Levy

Publications and source records attributed to J V Levy.

8 recordsLinked to original sources
PubMed1991

Effects of antiplatelet agents on platelet aggregation induced by platelet--activating factor (PAF) in human whole blood.

Impedance aggregometry was used to evaluate the potency of anti-platelet agents on Platelet Activating Factor (PAF)--induced platelet aggregation in citrated human whole blood. Drugs were tested for ability to inhibit maximum aggregation to PAF. Dose response curves were obtained and the concentration of drug producing 50% inhibition of maximum aggregation (ED50) determined. ED50's (microM) for specific PAF antagonists WEB 2086, Ro 19-3704, FR-900452, BN 52021, L-652,731, CV 3988, WEB 2118 and 48740 RP are: 0.39, 2.4, 4.7, 19.5, 21.0, 5.32, 161.0, 924.0, respectively. ED50's for non-specific PAF antagonists, diltiazem, propranolol, ketotifen, procaine HCL, and lidocaine HCL are: 38.0, 56.0, 250.0, 513.0 and 768.0, respectively. Ibuprofen was inactive at 2300 microM. Results are consistent with concept that there are specific receptors on platelets mediating PAF-induced aggregation in whole blood. Aggregation is inhibited potently by specific and competitive PAF receptor antagonists. Whole blood aggregometry may be a valid method for predicting in vivo activity of PAF antagonists.

Adolescent↗
PubMed1989

The benzodiazepine receptor ligands RO 5-4864 and RO 15-1788 do not block the inhibition of PAF-induced platelet aggregation seen with the hetrazepine WEB2086.

The hypothesis was tested that the hetrazepine WEB 2086 acts as an inhibitor of PAF-induced platelet aggregation via interaction with the platelet benzodiazepine receptor(BDZR). WEB 2086 is a potent inhibitor of rabbit platelet aggregation and ATP secretion induced by 370 nM PAF. The two BDZR ligands RO 5-4864 and RO 15-1788 (7-96 microM) are inactive as PAF antagonists. When platelets were pretreated with either BDZR ligand, and then exposed to various concentrations of WEB 2086, there was no alteration of the dose-response relationship of the hetrazepine on PAF-induced aggregation, as reflected by threshold concentration, ED50, or maximum inhibition seen with WEB 2086. Pretreatment of platelets with the BDZR ligands also failed to block the inhibitory action of WEB 2086 on PAF-induced ATP release. The data are consistent with the notion that WEB 2086 acts as a PAF antagonist through its action at a specific PAF receptor, and is dissociated from, and independent of, interaction with the benzodiazepine receptor.

Adenosine Triphosphate↗
PubMed1978

Contractile responses to prostacyclin (PGI2) of isolated human saphenous and rat venous tissue.

Prostacyclin (PGI2), in a wide concentration range, produced neither contraction nor relaxation of isolated human saphenous vein. Isolated portal veins and vena cava from normal and spontaneously hypertensive rats (SHR) responded only with an increase in contractile tension when exposed to PGI2. This constrictor effect was absent in a calcium-free buffer. PGI2 failed to relax KCI contracted vena cava. The constrictor effect of PGI2 on portal vein was attenuated in a glucose-free, oxygen deficient buffer. No tachyphylaxis or tolerance to the constrictor effect of PGI2 was noted. Results emphasize that PGI2 may produce differing effects on vascular smooth muscle tension depending on species and type of blood vessel studied.

Animals↗
PubMed1977

Changes in systolic arterial blood pressure in normal and spontaneously hypertensive rats produced by acute administration of inhibitors of prostaglandin biosynthesis.

Six non-steroidal agents having the property of being able to inhibit prostaglandin (PG) biosynthesis or action were tested for their ability to affect systolic blood pressure in unanesthetized normotensive (WKY) and Spontaneously Hypertensive Rats (SHR). In WKY and pre-hypertensive young SHR, s.c. injection of indomethacin (1.0 mg/kg) had no significant effect on blood pressure measured 30 minutes after injection. In older SHR, indomethacin (15 mg/kg) caused a significant pressor response, while in age-matched WKY, this dose had no significant effect. Indomethacin also showed a pro-hypertensive action in 10-14, 23-38 and 23-27 week old SHR with doses of 1.0 and 3.0 mg/kg, respectively. Tiaramide (5 mg/kg), ETYA (5 mg/kg), tolmetin (25 mg/kg), and meclofanamate (15 mg/kg) caused a significant elevation of blood pressure in mature (7-8 month old) SHR. Age matched WKY showed no significant response to the same doses of these four agents. Fenoprofen (75 mg/kg) caused a significant elevation in pressure in 12-13 weeks old SHR which persisted for at least 2 hours. Tiaramide had no significant effect on pre-hypertensive SHR. The results are consistent with the concept that inhibition of prostaglandin in synthesis may result in a diminished turnover of anti-hypertensive prostaglandins in SHR which are being elaborated in response to the hypertensive state. In normal rats and pre-hypertensive SHR, inhibition of prostaglandin synthesis or function may not result in a hypertensive response since pro-hypertensive factors either are absent, or other antihypertensive substances may still predominate to help maintain normal blood pressure.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1976

Beta-adrenergic receptor blocking drugs in spontaneous hypertension.

Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension.

Adrenergic beta-Antagonists↗
PubMed1975

Verapamil and diazoxide antagonism of agonist-induced contractions of aortic strips from normal and spontaneously hypertensive rats (SHR).

The vulnerability of aortic strips from 50-52 week old Spontaneously Hypertensive Rats (SHR) and normotensive Wistar-Kyoto (WKY) controls to the inhibitory or relaxing effects of the calcium antagonists verapamil and diazoxide was studied. Verapamil produced concentration-dependent inhibition (antagonism) of KCl, PGE2, and methoxamine-induced contraction of aortic strips from SHR and WKY. KCl and PGE2-induced contraction of SHR tissue were less readily antagonized by verapamil compared to WKY preparations. The reverse was seen with methoxamine-induced contraction. The slope of the verapamil inhibition curve of KCl-induced contraction was significantly steeper for aortic strips form WKY. Verapamil and diazoxide also produced concentration-dependent relaxation of KCl-induced contraction of aortic strips, no significant differences being noted in SHR and WKY responses. Results are compatible with the hypothesis that arterial smooth muscle from SHR is characterized by a more tightly bound pool or source of activator Ca++ which is released by certain agonists. Failure to observe a significant difference in verapamil or diazoxide induced relaxation of KCl contracted tissues from SHR or WKY suggests that in the tonic phase of KCl contraction, transmembrane fluxes of Ca++ in SHR and WKY are equally vulnerable to the Ca++ channel inhibitory effect of the antagonists.

Animals↗