Biomedical subjects

J Talesnik

Publications and source records attributed to J Talesnik.

At least 19 recordsLinked to original sources

PubMed1986

Arachidonic acid induced coronary reactions and their inhibition by docosahexaenoic acid.

The objective of the present study was to further investigate the influence exerted by docosahexaenoic acid (DHA) on the coronary reactions induced in isolated perfused hearts of rats and guinea pigs by bolus doses of arachidonic acid (AA). As in previous studies, we found that AA produced a coronary constriction followed by a longer lasting dilatation. The present data demonstrate that a 5-min infusion of DHA at 0.17-0.68 microM caused a concentration-dependent inhibition of the AA-induced constriction. The vasodilatation determined by AA was also depressed, but only after about 30 min of a sustained DHA infusion. The precursor of AA, linoleic acid (LA), was also infused for about 30 min, and like DHA it inhibited the coronary reactions induced by AA. LA is not converted into AA by the isolated heart, but like DHA, was probably incorporated into the cells of the coronary vascular compartment. It is known that LA, administered "in vivo" to mammals, is converted into AA and increases the production of eicosanoids, whereas DHA does not follow this metabolic pathway. The incorporation of these essential polyunsaturated fatty acids by the isolated perfused heart would inhibit the cyclooxygenase in the coronary vessel walls, interfering with the generation of vasomotor metabolites from AA. We postulate that the systemic administration of DHA, by inhibiting the synthesis of a constrictor metabolite, could be beneficial in reducing the damage due to microvascular constriction in myocardial ischaemia.

Animals↗

PubMed1986

Platelet antiaggregatory substances inhibit arachidonic acid induced coronary constriction.

Isolated perfused hearts of rats and guinea pigs reacted to arachidonic acid (AA) with coronary vasoconstriction followed by vasodilatation. The infusion of prostacyclin (PGI2), Iloprost, hydralazine (HYD), and nifedipine (NFP) elicited a vasodilatation that nullified the coronary flow reserve, therefore the AA-induced vasodilatation was abolished. Dipyridamole (DPY) and 1-methyl-3-isobutylxanthine (MIX) produced a slight coronary dilatation without restricting the dilatation induced by AA. Regardless of their vasodilator action, all these drugs acted by inhibiting the AA-induced coronary constriction, while their infusion lasted. We postulated that a thromboxane-like substance, formed from AA in the vascular walls, would be responsible for the coronary vasoconstriction caused by AA. The inhibition of the AA-induced coronary constriction by PGI2, Iloprost, HYD, NFP, DPY, and MIX may be explained by an inhibitory action of these drugs on the synthetic processes of the thromboxane-like substance.

1-Methyl-3-isobutylxanthine↗

PubMed1985

Modulation of positive inotropy and metabolic coronary dilatation by myocardial alpha-adrenoceptors.

Cardiac hyperactivity and its consequent metabolically induced coronary vasodilation (MCD) were studied in isolated, perfused, electrically paced rat hearts. The alpha-adrenoceptor agonists, phenylephrine and methoxamine, produced a concentration-dependent inhibition of the inotropic responses to noradrenaline, dobutamine, isoprenaline, tyramine, and glucagon, while relatively potentiating their MCD reactions. This inhibition was unrelated to the alpha-agonists' known inotropic action and was not affected by catecholamine depletion of the heart. Withdrawal of the alpha-agonists or administration of the alpha-adrenoceptor antagonists phentolamine, phenoxybenzamine, or prazosin returned the inotropic and MCD reactions to normal. Neither the MCD response to electrically induced tachycardia nor the inotropic reactions produced by calcium chloride were affected by alpha-adrenoceptor agonists or antagonists. Alone, alpha-adrenoceptor antagonists were shown to potentiate the inotropic responses to noradrenaline and isoprenaline while the MCD was relatively diminished. The responses to glucagon were unaltered by alpha-antagonists. We postulate that myocardial reactivity to sympathetic stimulation can be modulated through alpha-adrenoceptors by the inhibition of processes that mediate cardiostimulation at post-beta-adrenoceptor sites, together with facilitation of those leading up to MCD. Accordingly, this modulation would act to prevent ischaemic damage to the heart by acting to limit the inotropic responses to increasing sympathetic stimulation while maximizing the blood supply to the myocardium.

Animals↗

PubMed1984

Blockade of coronary reactions to arachidonic acid by glyceryl trinitrate and tranylcypromine.

Isolated perfused hearts of rats or guinea pigs reacted to bolus doses of arachidonic acid (AA) with a coronary constriction followed by a protracted vasodilatation phase. Glyceryl trinitrate (GTN; 55-95 microM) produced coronary dilatation during which the AA-induced constriction remained unaltered, or even enhanced. After 'acute tolerance' developed by sustained GTN infusion, the constrictor phase of AA was inhibited while the vasodilatation continued unaltered or slightly enhanced. Nitroprusside (Np; 5-56 microM) determined a coronary vasodilatation that persisted throughout its administration and appeared to be associated with an inhibition of the AA-induced coronary constriction. While withdrawal of Np resulted in an immediate recovery of coronary flow levels and of the reactions to AA, the blockade of AA-coronary constriction continued after GTN withdrawal. Tranylcypromine (TRC) infusion did not alter the basal coronary flow, but it produced a specific inhibition of the AA-induced coronary vasodilatation. We postulated that the blockade of the coronary constriction exerted during GTN acute tolerance would result from an inhibition of the synthesis of a constrictor metabolite (thromboxane-like substance?) formed in the coronaries through the cyclooxygenase metabolic pathway of AA.

Animals↗

PubMed1984

Enhancement by glutathione of the inotropic actions of catecholamines and glucagon.

We have previously shown that cardiostimulation produced by catecholamines, glucagon, tachycardia or CaCl2, resulted in a metabolically induced increase in coronary flow [9, 11, 12]. Slow infusion of prostaglandin E2 (PGE2) or its precursor, arachidonic acid, inhibited the development of metabolic coronary dilatation without major alterations of the effects of the cardiostimulating agents on the cardiac activity [9, 11, 12]. Since PGE2 synthesis is known to be enhanced by glutathione we thought that its addition to the perfused heart would intensify the inhibition of the metabolic coronary dilatation produced by arachidonic acid. While testing the influence of noradrenaline in the isolated perfused heart, we found that the inotropic action and the resulting coronary dilatation were markedly increased during glutathione administration. We diverted the investigation from its original purpose to further study this novel action of glutathione and we report here that catecholamines and glucagon inotropic effects, and resulting metabolic coronary dilatation are enhanced by glutathione. Neither the CaCl2 nor the coronary dilatations due to reactive hyperaemia or adenosine were altered by glutathione.

Animals↗

PubMed1984

Enhancement of metabolic coronary vasodilatation by nicotinic acid or amide.

Cardiostimulation produced by noradrenaline, glucagon, or tachycardia on the isolated perfused rat heart produced a metabolic coronary dilatation that was potentiated by nicotinic acid or its amide [NIC; 0.05-1.0 mM] without affecting the cardiostimulation. Reactive hyperaemia to brief coronary occlusion was unaffected by NIC, thus confirming that its vasodilator mechanism is of a different nature than that leading to metabolic coronary dilatation. It is suggested that NIC may be of significance as an adjuvant in the treatment of certain types of coronary insufficiencies.

Animals↗

PubMed1984

Reduced glutathione modulates the arachidonic acid induced coronary reactions.

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5-0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.

Animals↗

PubMed1982

Coronary flow reactions to arachidonic acid are inhibited by docosahexaenoic acid.

Arachidonic acid (AA) administered to isolated perfused rat hearts produced coronary vasoconstriction followed by vasodilatation due to biotransformation of AA into vasoactive metabolites. The formation of these metabolites may be blocked with ibuprofen or fenclorac. Slow infusions of docosahexaenoic acid (DHx) resulted in an inhibition of the coronary responses to AA. These results indicate that DHx behaves as a modulator of coronary responses elicited by AA metabolites.

Animals↗

PubMed1982

Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat.

The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25 mg/1) reversibly inhibited both phases of the response induced by AA. Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. Short infusions of acetylsalicylic acid at low concentrations (2.9 micrograms/ml), dipyridamole (0.6 micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively inhibited the vasoconstrictor phase of the response to AA. It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. Linolenic, linoleic, dihomo-gamma-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.

Animals↗

PubMed1980

Enhancement of noradrenaline-induced metabolic coronary dilatation by ethanol.

Isolated perfused rat hearts receiving noradrenaline as a cardiostimulatory agent show the characteristic metabolic coronary dilatations which correlate with the inotropic effect elicited by noradrenaline. Addition of ethanol (20-400 mg/dl) to the perfusion fluid produced a concentration-dependent enhancement of the metabolic coronary dilatation. The latter was increased by 50% at about 125 mg ethanol/dl. Since the inotropic responses to noradrenaline were not affected by ethanol it is suggested that alcohol produces an alteration in the system that normally adapts the coronary flow to an increased cardiac performance. The effect of ethanol was fully reversible; removal of alcohol from the perfusion fluid restored the metabolic coronary dilatation in response to noradrenaline to control values. At high concentrations, 200-400 mg/dl, ethanol produced a small but significant reduction in contractility of the myocardium (11.1 +/- 2.4%). At these concentrations ethanol enhanced the noradrenaline induced metabolic coronary dilatation by about 100%. These data indicate that ethanol at concentrations that are commonly found in blood in vivo may be beneficial in facilitating the coronary reactions during cardiac exertion. However cardiodepressant effects, particularly at higher concentrations, must also be considered.

Animals↗

PubMed1979

Myocardial synthesis of prostaglandin-like substances and coronary reactions to cardiostimulation and to hypoxia.

1 Continuous recording of cardiac contractions and coronary flow from isolated perfused hearts of rats permitted the study of coronary reactions to: (a) cardiostimulation induced by single doses or slow infusions of noradrenaline, CaCl2, glucagon or electrically induced tachycardia; (b) short interruptions of coronary inflow (hypoxia). 2 Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing. 3 Metabolic coronary vasodilatation (MCD) resulting from cardiac hyperactivity induced by noradrenaline, Ca2+, tachycardia or glucagon was inhibited by administration of prostaglandin E2. Reactive hyperaemia response to hypoxia was unaffected by prostaglandin administration. 4 Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 X 10(-7) M), presumably by its conversion into prostaglandin-like substance since arachidonic acid failed to block MCD in hearts from rats pretreated with non-steroidal anti-inflammatory drugs (indomethacin, naproxen, phenylbutazone). 5 Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin-like substances by anti-inflammatory drugs. 6 Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not advocate prostaglandin-like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity. 7 We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?).

Animals↗

PubMed1977

Coronary reactions to cardiac hyperactivity and to hypoxia in isolated perfused heart of rat.

1. Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2. The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3. In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4. Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. 5. Coronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2.6. Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7. Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8. We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.

Animals↗

PubMed1976

Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity.

In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3',5'-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (pge2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents.

Animals↗

PubMed1974