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Paradoxical calcium action on some cardiovascular verapamil effects
j Mol Cell Cardiol 18 (Supplement 3) (1986) COMPARTMENTED AMP IN GUINEA P:G CARDIAC MUSCLE. R. Sunset, D. Hartman, R. Mallet, Dept. Physiology, Unlformed Services University, Bethesda, MD. The thermodynamic state of the cytosolic ATP-ADP system (as judged by cmeatlne kinase equilibrium in normoxic hearts perfused at constant workloads and steady energy-yielding metabolic rates) requires an obligatory association between sti~lated oxygen uptake (M~02) and decreased free cytosolic [ATP]/[ADP] ratio concomitant with an increase in the concentration of free ADP([ADP])(Eur. J. Biochem., in press)- Estimates of [ADP] place its values between 16 to 60 ~M as a function of energy utilization. Such low free [ADP] predict cytosolic free ~MP ([AMP]) levels in the B5 to 750 nanomolar range in normo• and low flow ischemic hearts, resp.(prescribed by mass action equation of myokinase reaction). Measured total cardiac AMP content was 2 to 3 orders of magnitude hiRher than cytosollc [AMP]. Thus, free cytosollc ~MP accounted for about I% of total AMP, implyin~ that AMP is highly compartmented and that most of cardiac AMP is bound and/or located in the mitoehondria, even during low flow ischemia. The apparent submicromolar levels of cytosoIic [AMP] place control of AMP deRradatlon to inosine and vasodilator adenosine pro• to 5'-nucleotldase and adenylate deamlnase, resp.; this minimizes, but does not exclude allosteric interactions. Thermodynamic control of free [AMP] can also render the free adenylateadenosine system highly adaDtlve to imbalances between .ti|ization and production of ATP produced by states of oxy~en-deficlenev. Supported by NIH NL2q060 and II~H~S R0763~.
PARADOXICAL CALEI~4 ACTION ON SOME CARDIOVASCULAR VERAPAMIL EFFECTS. M.C. C a m i l i ~ de Hurtado, O.A. Gende, ~.E. Cingolanl. Centr~ de Investlgaclones Cardlovasoulal~sS, Faoultad de Cienelas M~dlcas, LB Plata, ArEentina. The ability of calclum infusions to reverse some cardlovasoular effects of verapam~l was tested in anesthetized rats and on isolated rat atria. Intravenous infUsions of 1.88 mg/kg verapamll decreased mean arterial pressure (Pa) and heart rate (HR) and prolonged PR interval (PRI). ^After these effects were stabilized a seEies of infUsions of calcium_ehlorJde (Ca ~+) (338 pmoles/k~ each) were performed. Ca ~§ on the one band returned Pa to its basal value, on the other band, failed to reverse the effect of verapamll on PRI and the first infusion of Ca ~§ pr~duee~an addltional decrease in l~R by 32 • 5 beets/min. This paradoxical effect of Ca-" was prevented by pr~vlous infusion of atropine (0.2 ~+A~i). On isolated atria the increase of extracellular CaL+ concentration ( ICe Io) from 1.0 to 6.0 mmoles/1 increased atrial rate by about 40 beats/~n, both in atr~pinlzed and in non-atropinlzed preparations. After verapam11, however, tbe same increase in decreased atrial rate in 50 ~ 15 beats/mln in non-atropinlzed atria. The results obtained indicate that extra calcium can overcome the hypotensive effect of verapamil, whereas paradoxically increases its negative ohronotroplc effect and fails to reverse its effect on AV conduction. Th~s paradoxlcal effect of calclum can he prevented, both in vivo and in vitro, by atropine blockade of muscarlnlc receptors.
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CHANGES IN MYOCYTESIZE DURING REVERSAL OF THYROID-INDUCED CARDIAC HYPERTROPHY. S.E. Campbell and A.M. Gerdes, Dept. of Anatomy, Univ. of South Florida, Tampa, FL. Previous reports stated that cardiac hypertrophy in adult rats was completely reversed two weeks after cessation of experimental hyperthyroidism. To investigate regional changes in cell size during thyroid reversal, adult Sprague Dawley rats were treated with 0.6% desiccated thyroid (mixed with food). Isolated myocytes were prepared by retrograde coronary perfusion with collagenase after lO weeks of treatment. Additional isolations were done at various times post-treatment. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured d i r e c t l y , and crosssectional area (CSA) was calculated from V/L. Heart weight increased 42% after lO weeks of thyroid treatment (p
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PARADOXICAL CALEI~4 ACTION ON SOME CARDIOVASCULAR VERAPAMIL EFFECTS. M.C. C a m i l i ~ de Hurtado, O.A. Gende, ~.E. Cingolanl. Centr~ de Investlgaclones Cardlovasoulal~sS, Faoultad de Cienelas M~dlcas, LB Plata, ArEentina. The ability of calclum infusions to reverse some cardlovasoular effects of verapam~l was tested in anesthetized rats and on isolated rat atria. Intravenous infUsions of 1.88 mg/kg verapamll decreased mean arterial pressure (Pa) and heart rate (HR) and prolonged PR interval (PRI). ^After these effects were stabilized a seEies of infUsions of calcium_ehlorJde (Ca ~+) (338 pmoles/k~ each) were performed. Ca ~§ on the one band returned Pa to its basal value, on the other band, failed to reverse the effect of verapamll on PRI and the first infusion of Ca ~§ pr~duee~an addltional decrease in l~R by 32 • 5 beets/min. This paradoxical effect of Ca-" was prevented by pr~vlous infusion of atropine (0.2 ~+A~i). On isolated atria the increase of extracellular CaL+ concentration ( ICe Io) from 1.0 to 6.0 mmoles/1 increased atrial rate by about 40 beats/~n, both in atr~pinlzed and in non-atropinlzed preparations. After verapam11, however, tbe same increase in decreased atrial rate in 50 ~ 15 beats/mln in non-atropinlzed atria. The results obtained indicate that extra calcium can overcome the hypotensive effect of verapamil, whereas paradoxically increases its negative ohronotroplc effect and fails to reverse its effect on AV conduction. Th~s paradoxlcal effect of calclum can he prevented, both in vivo and in vitro, by atropine blockade of muscarlnlc receptors.
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CHANGES IN MYOCYTESIZE DURING REVERSAL OF THYROID-INDUCED CARDIAC HYPERTROPHY. S.E. Campbell and A.M. Gerdes, Dept. of Anatomy, Univ. of South Florida, Tampa, FL. Previous reports stated that cardiac hypertrophy in adult rats was completely reversed two weeks after cessation of experimental hyperthyroidism. To investigate regional changes in cell size during thyroid reversal, adult Sprague Dawley rats were treated with 0.6% desiccated thyroid (mixed with food). Isolated myocytes were prepared by retrograde coronary perfusion with collagenase after lO weeks of treatment. Additional isolations were done at various times post-treatment. Cell volume (V) was measured with a Coulter Channelyzer, cell length (L) was measured d i r e c t l y , and crosssectional area (CSA) was calculated from V/L. Heart weight increased 42% after lO weeks of thyroid treatment (p
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