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Biomedical subjects

J V Levy

Publications and source records attributed to J V Levy.

At least 37 records · Page 2Linked to original sources
PubMed1982

Effect of isosorbide dinitrate and its metabolites on rabbit atrial myocardial force-frequency relationships in vitro.

Isosorbide dinitrate (ISDN) and its two mononitrate metabolites were studied for their effects on the force-frequency relationship of isolated rabbit left atrial preparations. ISDN (4.9 and 15 microgram/ml) (50-150 times maximum therapeutic plasma concentrations) produced no significant effect on the frequency-dependent changes in contractile force. A concentration of 90 micrograms/ml (approximately 900 times therapeutic concentrations) produced a depression of contractility normally observed at frequencies of 80-400 beats/min. The two mononitrate metabolites of ISDN (endo- and exo-nitratoisosorbide) (90 micrograms/ml and 450 micrograms/ml) failed to alter the normal-force-frequency relationship over the range of 10-400 beats/min. These concentrations are several thousand times greater than plasma levels achieved in man with therapeutic dosing of ISDN. The basic lack of effect of ISDN and its metabolites on this fundamental property of myocardial contractility under the test conditions suggests that their therapeutic action is not mediated through direct effects on myocardial excitation-contraction coupling mechanisms.

Animals↗
PubMed1980

Prostacyclin-induced contraction of isolated aortic strips from normal and spontaneously hypertensive rats (SHR).

Prostacyclin (PGI2) (500-5,000 ng/ml) produced a concentration-dependent increase in contractile tension of isolated thoracic aortic strips (AS) from normotensive (WKY) and spontaneously hypertensive rats (SHR). No significant differences were noted between this response to PGI2 in these two groups. Lower concentrations of PGI2, (10 pg/ml - 100 ng/ml) caused neither contraction nor relaxation of agonist-contracted tissue. PGI2 (500-5,000 ng/ml) did not relax KCl or methoxamine contracted AS. In concentrations above 100 ng/ml, PGI2 caused a further increase in tension in KCl-depolarized preparations. The constrictor effect of PGI2 on AS was attenuated by verapamil pretreatment or removal of extracellular Ca++ from the physiological buffer. This inhibitory effect of Ca++ deficiency on the PGI2 response was significantly greater in AS from SHR compared to WKY tissue. The stable metabolite of PGI2, 6-keto PGF1a, caused a weak constrictor effect (40% of KCl reference contraction) over the concentration range 1,000-5,000 ng/ml. Contraction induced by PGI2 was not prevented by pretreatment with antagonists of adrenergic, histamine, serotonin or cholinergic receptors. The contraction response of the rat AS to PGI2 is similar to that reported for porcine coronary artery and rabbit aortic tissues in vitro.

Animals↗
PubMed1980

Cinepazet relaxation of aortic strips from normal and spontaneously hypertensive rats.

The vasodilator cinepazet (Vascoril) was tested for its ability to relax potassium-contracted aortic strips obtained from normal and spontaneously hypertensive rats (SHR). Cinepazet caused a dose-dependent relaxation of the isolated aortic strip preparations which had been contracted with 60 mM KCl. The ED50 for this relaxant effect was 200 microgram/ml. No differences in relaxation response to cinepazet were found between tissues from SHR and normal animals. The drug is 2 x 10(4) less potent than verapamil on a weight basis in this action on rat aortic tissue. The results suggest that the excitation-contraction mechanism associated with KCl-induced membrane depolarization is equally affected by cinepazet in aortae from SHR and WKY.

Animals↗
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↗
PubMed1972

Effect of synthetic bradykinin on contractile tension of human saphenous vein strips.

The ability of synthetic bradykinin to contract isolated, helically-cut human saphenous vein strips was studied in vitro. Bradykinin (0.05-2.0,mug/ml) consistently failed to contract human vein strips. Similarly prepared rabbit aortic strips also failed to contract when exposed to bradykinin in the concentration range studied. Bradykinin-insensitive vein and aortic strips responded with substantial increases in contractile tension when exposed to prostaglandin E(2), noradrenaline, histamine and KC1. However, bradykinin (0.1,mug/ml) was, capable of relaxing human vein strips, which had contracted in response to prostaglandin E(2).

Animals↗