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Biomedical subjects

S Kalsner

Publications and source records attributed to S Kalsner.

At least 73 records · Page 4Linked to original sources
PubMed1977

The effect of hypoxia on prostaglandin output and on tone in isolated coronary arteries.

The relationship between bath Po2, intramural prostaglandin synthesis, and vessel tone in isolated coronary arteries of cattle was studied. The basal output of prostaglandin under 95% O2-5% CO2 (580 mmHg) was elevated markedly when the Po2 was decreased to 47 mmHg but extreme hypoxia (9 mmHg) sharply curtailed output. The coronary vessels responded to 47 mmHg with relaxation but they contracted when the Po2 was decreased further to 9 mmHg. Known inhibitors of prostaglandin synthesis attenuated both the hypoxia-induced relaxations and contractions. Analysis of the effects of extreme hypoxia and of inhibitors of prostaglandin synthesis on tone indicated that both suppress prostaglandin production. It is concluded that coronary prostaglandin synthesis is accelerated by hypoxia unless the oxygen deprivation is so severe as to limit the availability of oxygen for synthesis.

Animals↗
PubMed1976

The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.

Animals↗
PubMed1976

Sensitization of effector responses by modification of agonist disposition mechanisms.

Much confusion arises in the field of agonist-effector supersensitivity phenomena due to the often encountered lack of discrimination between agonist disposition mechanisms functioning, in the system under study, as access barriers and as terminating mechanisms. Access barriers limit agonist approach to the receptor region and terminating mechanisms serve to remove agonist from the site of action. The assumption of a quantitative identity in these two functions is not often warranted and the effects inhibition of these processes have on the magnitude of effector responses and on their duration can differ strikingly, both qualitatively and quantitatively.

Animals↗
PubMed1976

Intrinsic prostaglandin release. A mediator of anoxia-induced relaxation in an isolated coronary artery preparation.

Isolated coronary artery strips of the bovine heart in vitro relax in response to decreased bath oxygen tensions (from 515 mm Hg to 112, 53, and 38 mm Hg). In addition, the rate of intrinsic formation and release of prostaglandin is considerably increased under conditions of decreased PO2. The vascular relaxations under reduced PO2 are attenuated and the elevations in prostaglandin output blocked by prostaglandin synthesis inhibitors. It appears that alterations in the output of a PGE with vasodilator activity, probably E1, is a significant factor regulating the compensatory changes in tone of the coronary arteries in response to anoxic conditions.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1975

Adenosine and dipyridamole actions and interactions on isolated coronary artery strips of cattle.

1 The actions and interactions of adenosine and dipyridamole were investigated on isolated strips of coronary arteries of beef cattle. It was found that small diameter arteries (about 0.5-1.0 mm o9d.), raised to a moderate level of tone with potassium, responded with relaxation to low concentrations of adenosine. 2 Dipyridamole, over a broad concentration range (6.0 X 10(-8)-2.0 X 10(-5)M), enhanced these responses, shifting the adenosine concentration-response curve (3.7 X 10(-8)-1.1 X 10(-4)M) considerably to the left. In contrast, inhibitory concentrations-response curves to sodium nitrite and to noradrenaline were not materially altered by dipyridamole. 3 Studies of the uptake of [3H]-adenosine revealed a rapid uptake of the nucleoside by coronary artery strips, which was inhibited by dipyridamole (6.0X 10(-8)-2.0X10(-5)M); but this may not be sufficient to account fully for the observed sensitization. 4 It is concluded that the regulation of adenosine responses and the action of dipyridamole in the heart involve a more direct association with coronary vascular tissue than has been previously appreciated.

Adenosine↗
PubMed1975

Role of extraneuronal mechanisms in the termination of contractile responses to amines in vascular tissue.

1 The role of the uptake and release of agonist from extraneuronal sites in the termination of responses of rabbit aortic strips to amines was studied. 2 Strips were contracted with adrenaline or noradrenaline and after response plateau was reached, the muscle chambers were washed free of agonist and the relaxation in Krebs solution recorded. After inhibition of catechol-O-methyl-transferase, monoamine oxidase and neuronal uptake the relaxation rate was greatly prolonged. Evidence is provided that this very slow relaxation resulted from the accumulation of intact amine at extraneuronal sites during exposure to the agonist and its subsequent release past receptors due to a reversal of the concentration gradient after washout. 3 Pretreatment with the haloalkylamine, GD-131 (N-cyclohexylmethyl-N-ethyl-beta-chloroethylamine), an inhibitor of extraneuronal uptake, returned the slow relaxation rate after enzyme inhibition towards that of control strips. By blocking the extraneuronal transport of amines their accumulation at intracellular loci after enzyme inhibition was prevented. 4 The effects of GD-131 and 17beta-oestradiol on the relaxation rate of untreated strips contracted by adrenaline and noradrenaline confirmed that extraneuronal uptake to sites of enzymatic activity is the major mechanism terminating their action. 5 Inactivation of extraneuronal transport sites by GD-131 was prevented by protecting them with 17beta-oestradiol or normetanephrine during exposure to the haloalkylamine, pointing to a common site of action of these agents on a specific carrier system for amines. 6 Evidence is presented that the relaxation from contractions induced by histamine and 5-hydroxytryptamine also involves extraneuronal accumulation and release, probably by an uptake process which is identical to the one for catecholamines.

Amines↗
PubMed1975

Endogenous prostaglandin release contributes directly to coronary artery tone.

An in vitro coronary artery preparation of beef heart was found to synthesize and release continuously large amounts of a prostaglandin of the E type. Inhibition of prostaglandin synthesis with aspirin, indomethacin, or eicosa-5,8,11,14-tetraynoic acid induced a sustained contraction of the coronary artery, and pretreatment with indomethacin diminished markedly the output of prostaglandin into the bathing medium. It appears that prostaglandin E1, generated from within the vessel wall itself, may act as an intrinsic regulator of coronary artery tone in the beef heart, and that blockade of this function leads to vasospasm.

Animals↗
PubMed1975

Mechanism of methylxanthine sensitization of norepinephrine responses in a coronaryartery.

Beta-adrenergic receptor-mediated relazation to norepinephrine was enhanced by caffeine amd aminophylline in a coronary artery preparation of the beef in vitro. Augmented responses were not obtainable in the presence of known inhibitors of the extraneuronal uptake and metabolism of norepinephrine, estradiol-17beta, and the haloalkylamine GD-131, which themselves potentiate responses. In addition, the effect on the norepinephrine dose-response curve of the combination of a methyixanthine and U-0521,the latter a potent inhibitor of catechol O-methyltransferase, the major enzyme of catecholamine inactivation in vascular tissue, did not differ from that of U-0521 alone. Studies of the extraneuronal accumulation of '3H-labeled norepinephrine revealed that caffeine and aminophylline, along with the known inhibitors, materially reduced theaccumulation of label in coronary tissue. It is concluded that the methylxanthinesenhance beta-adrenergic receptor-mediated responses via a blockade of catecholamine uptake, giving rise to an increased concentration of agonist at receptors, and not by an action linked to cyclic AMP accumulation, consequent to receptor activation.

Aminophylline↗
PubMed1974

A vasodilator innervation to the central artery of the rabbit ear.

1 The possibility of a vasodilator innervation to the isolated and perfused central artery of the rabbit ear was examined.2 Stimulation of the periarterial nerves in the presence of noradrenaline or other agonist used to maintain a partial constriction of the ear artery, led to a decrease in intraluminal flow followed after the cessation of stimulation by an increase in flow beyond the pre-stimulation level.3 After blockade of adrenergic transmission with bretylium or guanethidine or of the alpha- and beta-adrenoceptors with phentolamine and propranolol, stimulation of the periarterial nerves in the presence of a background tone, led to a clearly detectable vasodilation. This dilatation was not blocked by treatment with atropine or mepyramine; nor was it enhanced by physostigmine.4 Pretreatment of rabbits with reserpine (2 mg/kg) to deplete catecholamine stores, eliminated both the vasoconstrictor and vasodilator responses to nerve stimulation. However, a lower dose of reserpine (0.2 to 0.5 mg/kg) selectively eliminated the vasoconstrictor component of periarterial nerve activation.5 The ear artery dilated in response to low concentrations of prostaglandin E(1), and E(2), in the presence of noradrenaline, but treatment with inhibitors of prostaglandin synthesis, indomethacin, aspirin or eicosa-5,8,11,14-tetraynoic acid did not reduce the vasodilator response. Attempts to extract a prostaglandin in the bathing medium were unsuccessful.6 The involvement of a purine nucleotide appeared unlikely since the ear artery dilated only in response to fairly high concentrations of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP). Furthermore, dipyridamole, an inhibitor of adenosine uptake, enhanced dilation due to exogenous ATP but not to periarterial nerve stimulation.7 It is concluded that the central artery of the rabbit ear has a vasodilator innervation but the identity of the transmitter remains to be established.

Animals↗
PubMed1974

A new approach to the measurement and classification of forms of supersensitivity of autonomic effector responses.

1 It is proposed that sensitizations of autonomic effectors to agonists by drugs or procedures be considered in two main categories: those involving changes in the effective concentration of agonist at receptors (type I) and those involving changes in the responding tissue beyond the initial combination of agonist and receptors (type II). Type I sensitizations are appropriately described by determining the dose-ratio (horizontal shift of the dose-response curve) and type II sensitizations by assessing the change in the magnitude of the response.2 The inadequacy of the dose-ratio in assessing sensitizations related to an altered physiology of the responding tissue is illustrated by means of hypothetical examples with particular reference to the slopes of dose-response curves and altered maximal responses.3 An evaluation of the enhancement of responses of rabbit aortic strips to agonists by reserpine indicates that it is a type II sensitization. The shifts of dose-response curves to noradrenaline, isoprenaline, normetanephrine and 5-hydroxytryptamine after reserpine-treatment, were described both by the dose-ratio and by the increment in the magnitude of the response at various contraction amplitudes. The dose-ratio varied unpredictably for each agonist depending on the response level selected for comparison and also varied between agonists. However, the mm increment in response magnitude after reserpine approximated a constant value. Responses to potassium which by horizontal procedures were assessed among the least increased, were found to be enhanced the most when considered as a type II sensitization.4 It is concluded that both type I and type II procedures should be applied when dealing with an unidentified sensitization and that the data be critically assessed. The appropriate use of these procedures can aid in identifying and clarifying sensitizations, as well as in elucidating the sequence of steps between receptor activation and response in an effector.

Animals↗
PubMed1973

Mechanism of potentiation by amines of non-equilibrium blockade of the alpha-adrenoceptor.

1. The mechanism by which sympathomimetic and certain other amines enhance blockade of the alpha-adrenoceptors by the non-equilibrium antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in strips of rabbit aorta was examined.2. Non-equilibrium blockade of the 5-hydroxytryptamine receptors by EEDQ was not increased by sympathomimetic amines and was decreased by 5-hydroxytryptamine.3. Low concentrations of reversible competitive antagonists appeared to protect selectively against the additional blockade by EEDQ which develops in the presence of an amine.4. Phenoxybenzamine potentiated EEDQ blockade of the alpha-receptors but not of the 5-hydroxytryptamine receptors.5. Augmentation of EEDQ blockade was also detected in a variety of other tissues, but not in segments of rabbit intestine where alpha-adrenoceptors mediate an inhibitory response.6. It was concluded that EEDQ acts at two sites in antagonizing alpha-receptor mediated responses, and that one of these sites (site II) is separate from the site of action of agonists and phenoxybenzamine (site I). Amines which enhance blockade appear to exert their action by combining with a third site (site III), which may induce a conformational alteration at site II.7. It appears that the alpha-adrenoceptor may have multiple sites for drug interaction.

Amines↗
PubMed1972

Effects of the inhibition of noradrenaline uptake and synthesis on the maintenance of the response to continuous nerve stimulation in the central artery of the rabbit ear.

1. The central artery of the rabbit ear was perfused through its lumen in vitro, with a constant pressure technique, and stimulated continuously via its periarterial sympathetic nerves at the physiological frequency of 5 Hz.2. The vasoconstrictor response, which led initially to an almost complete cessation of intraluminal flow, deteriorated steadily over a period of hours. The involvement of presynaptic mechanisms in this effect was indicated by the finding that noradrenaline, administered extraluminally, produced a similar response before the onset of continuous stimulation and at a late stage when the constriction had decreased markedly. In addition, the noradrenaline precursor DOPA, restored the depressed responses towards their original values, indicating that failure involved depletion of mediator for release.3. Responses to continuous stimulation declined significantly faster after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine. However, inhibition of the uptake of noradrenaline with cocaine did not enhance the decline of the response, even when the sensitization produced by the compound was taken into account.4. It is concluded that synthesis, along with the mobilization of stored mediator, rather than uptake and re-use of noradrenaline maintain the effector response in the central artery of the rabbit ear stimulated continuously at a frequency within the physiological range.

Animals↗