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Biomedical subjects

F R Goodman

Publications and source records attributed to F R Goodman.

53 records · Page 3Linked to original sources

Alteration by phosphatidyl serine of tension responses and 45Ca distribution in aortic smooth muscle.

The effects of phosphatidyl serine (PS) on 45Ca distribution, 45Ca movements and contractions were examined in rabbit aortic smooth muscle. Contractile responses to submaximal concentrations of norepinephrine and histamine were potentiated by prior exposure to PS, but equivalent responses to potassium were unaffected. Addition of PS to the incubation solution decreased 45Ca uptake; exposure of aortic strips to PS during washout of either 45Ca or promethium (147Pm) resulted in maintained increases in efflux. These PS-induced alterations in net loss of 45Ca or 147Pm can be attributed to a decreased membrane reuptake and/or rebinding. However, the presence of PS during the washout significantly reduced the increases in 45Ca efflux rate elicited with either 0.05 mM concentrations of Ca++ or ethylenediamine tetraacetic acid. Thus, in rabbit aortic smooth muscle, exogenous PS can alter the availability and/or exchangeability of a membrane-bound Ca++ fraction. By specifically increasing the affinity for Ca++ at relevant membrane sites or stores. PS may enhance the ability of vascular smooth muscle to respond to stimulatory agents that mobilize Ca++ from these sites and, in this manner, potentiate contractile responses.

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Effects of neomycin on 45Ca binding and distribution in canine arteries.

The effects of neomycin (7.0 mM) on 45Ca movements and distribution were investigated in canine aortae and in canine carotid and terminal mesenteric arteries. Uptake of 45Ca was measured in calcium-free solution; the 45Ca tissue spaces in the carotid and terminal mesenteric arteries were 2--4 times greater than those observed in the aorta. Exposure of the aortae and the terminal mesenteric arteries to 1.5 mM Ca++ during the washout elicited large increases in 45Ca efflux in both preparations (increase in terminal mesenteric greater than aorta). Moreover, in all three arterial preparations, neomycin reduced 45Ca uptake and induced a sustained increase in 45Ca efflux (effects on terminal mesenteric larger than or equal to carotid greater than aorta). The terminal mesenteric and carotid arteries may accumulate and bind 45Ca at superficial membrane sites (readily exchangeable 45Ca) to a greater degree than does the aorta. If Ca++ located at these membrane sites contributes directly to the maintenance of mechanical responsiveness, then agents which alter membrane binding of Ca++ (e.g. neomycin) may exert a stronger action on these highly reactive vessels. Thus, contractile responsiveness in peripheral arteries may depend upon depots of superficially bound Ca++ to a greater degree than in the more centrally located aorta.

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Differential inhibitory effect of neomycin on contractile responses of various canine arteries.

The influence of neomycin on vascular smooth muscle contractile responses was examined in different isolated arterial preparations of the dog. Prior exposure (5 minutes) to 7 mM neomycin decreased contractile responses elicited with norepinephrine (NE, 0.6 muM) or KC1 (K-+, 80 nM) in helical strips of canine aortae (Ao) and femoral (F), carotid (Cd), renal (R), superior mesenteric (Sm), terminal mesenteric (Tm) and coronary (Cr) arteries. Addition of neomycin subsequent to NE-induced contractile responses depressed tension responses of the F, Cd, R, Sm and Tm arteries but had little or no effect on the Ao. However, after contractions had been elicited with K-+, neomycin had no effect on tension responses of the Ao, F, Cd, R or Sm arteries but depressed contractions of the Cr and Tm arterial strips. Preincubation with neomycin (0.7-3.5 mM) produced a concentration-related inhibition of contractile responses elicited in Tm arterial strips by addition of calcium ions (Ca-++; 1.6 mM) to a Ca-++-free depolarizing solution; conversely, subsequent addition of neomycin had no effect on maintained Ca-++ contractures. In constant flow-perfused terminal mesenteric arterial branches, neomycin (0.5-4.0 mM) produced a concentration-related antagonism of pressor responses elicited with NE (1-8 mug) or K-+ (40 mM). The inhibitory action of neomycin on K-+-induced pressor responses was inversely related to the Ca-++ concentration of the perfusion fluid. However, inhibition of NE pressor responses by neomycin did not appear to be related to the Ca-++ concentration. The differential inhibitory action of neomycin on contractions induced by NE and K-+ in various canine arteries suggests that different vascular beds vary in the manner in which Ca-++ is bound and subsequently utilized by stimulatory agents to elicit tension changes.

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Interactions between several rare earth ions and calcium ion in vascular smooth muscle.

The effects of lutetium (Lu+++), europium (Eu+++) and neodymium (Nd+++) on 45Ca distribution, 45Ca movements and contractions were examined in rabbit aortic smooth muscle. Tension responses to norepinephrine were markedly inhibited by all three rare earth ions; K+-induced responses and those to histamine were partially blocked. Addition of 1.5 mM Lu+++, Eu+++ or Nd+++ to the bathing solution reduced 45Ca uptake (Nd+++ greater than Eu+++ greater than greater than Lu+++), produced a maintained increase in 45Ca efflux from strips of media-intimal layer washed out in a 0-Ca++ solution (Nd+++ greater than Eu+++ greater than Lu+++), and, when present during 45Ca incubation (before 45Ca washout), altered the release of 45Ca elicited by addition of 1.5 mM Ca++ during the 45Ca washout (inhibition by Nd+++ greater than Eu+++ greater than Lu+++). The 3-fold greater uptake of 45Ca in a 0-Ca++ and 1.5 mM Lu+++ solution than in an equivalent Sr++ solution results from a decreased effect of Lu+++ upon the slower 45Ca washout component. The actions of Lu+++ were quantitatively similar to those of low La+++ concentrations (0.05-0.10 mM), whereas those of Nd+++ and Eu+++ resembled effects obtained with equimolar concentrations of La+++. Thus, the three rare earth ions produce qualitatively similar alterations in 45Ca uptake and superficial binding. The difference observed can be attributed to variations in their affinity for superficial Ca++ binding sites and in their ability to block Ca++ uptake.

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Effects of metiamide on distribution of 14C-histamine in aortic smooth muscle.

The effects of metiamide on 14C-histamine movements and on contractions induced by histamine were studied in rabbit aortic smooth muscle. Low temperature (0 degrees C) and pretreatment with aminoguanidine or chloroquine markedly reduced the uptake of 14C. Component analysis of 14C efflux curves indicated that this decrease occurred mainly within the slower of two washout components. Addition of metiamide (but not pyrilamine) to the bathing solution decreased 14C-histamine uptake, and exposure to metiamide during the washout of 14C-histamine decreased the rate of efflux. These effects of metiamide on 14C-histamine movements can be explained in terms of an altered ability of rabbit aortic smooth muscle to accumulate histamine at some cellular site or store.

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Alteration of contractile function and calcium ion movements in vascular smooth muscle by gentamicin and other aminoglycoside antibiotics.

Experiments were conducted to examine the effects of certain aminoglycoside antibiotics on contractile responses and related calcium ion (Ca(2+)) movements in isolated vascular smooth muscle. Gentamicin, kanamycin, and streptomycin decreased contractile responses produced by norepinephrine, histamine, and high K(+) in rabbit aortic strips. The inhibitory action of these antibiotics on mechanical function was more pronounced when the Ca(2+) concentration of the bathing solution was decreased from 1.5 mM (normal Ca(2+) solution) to 0.05 mM (low Ca(2+) solution). The uptake of radiocalcium ((45)Ca) into the isolated media-intimal layer of rabbit aortae was decreased in a maintained manner by each antibiotic. With gentamicin, the inhibitory effect on (45)Ca uptake was shown to be dependent upon the concentration of gentamicin employed and to be more evident in a 0.1 mM Ca(2+) solution than in a normal Ca(2+) solution. In addition, the rate of (45)Ca efflux from the rabbit aortic media-intimal layer was increased in a sustained manner by gentamicin, streptomycin, and kanamycin. Furthermore, contractile responses induced by high K(+) and norepinephrine in canine carotid arterial strips were inhibited by gentamicin. Present findings indicate that aminoglycoside antibiotics interfere with Ca(2+)-linked events leading to activation of the contractile mechanism of vascular smooth muscle. These in vitro findings may partially explain the occurrence of in vivo cardiovascular depression that has occasionally been observed after the administration of chemically related antimicrobial agents.

Aminoglycosides↗

Effects of hypertonic mannitol on contractile responses and 45Ca movements in isolated canine arteries.

The effects of hyperosmotic mannitol on vascular smooth muscle contractile responses and on 45Ca movements were examined in different isolated canine arteries. Prior exposure to 50 mM mannitol decreased contractile responses elicited with dopamine (DA) in helical strips of canine terminal mesenteric arteries (Tm) and decreased the contractile response elicited with potassium (K+) in both isolated left anterior descending (LAD) and circumflex coronary arteries. Tension responses induced by norepinephrine or DA in the Tm and K+ and prostaglandin F2 alpha in LAD were relaxed by subsequent exposure to mannitol. Mannitol increased the uptake of 45Ca in Tm arteries. Exposure of the Tm and branches of the LAD to mannitol during the washout of 45Ca resulted in a decrease in the rate of loss of 45Ca; the presence of either K+, Mg2+, or ethylenediamine tetraacetic acid during the washout did not prevent the observed mannitol-induced decrease in 45Ca efflux. These effects of mannitol on 45Ca efflux without a concomitant major change in net 45Ca uptake could be attributed to an increase in bound Ca2+ at relevant membrane sites or stores. Thus, hypertonic mannitol may alter contractile responsiveness of selected canine arteries by impeding the release of bound and/or sequestered Ca2+ and, in this manner, decreasing the Ca2+ concentration at the contractile elements.

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