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Density and affinity of specific ouabain binding in isolated neonatal and adult ventricular myocytes
J Mol Cell Cardiol 24 (Supplement
III) (1992)
p88ENsrmrANDMFlNITYCFSPECIFICCU?=UNBINLXEINISCIMED~?iNDADuup rBwl!BImm IceMeth W. Hewett, Kylie Wz&in, EYancis G. spinale, Christine E. Williamson, Paul C. Gillette. radical rrniversity of south Carolina, Division of pediatric cardiology, Charleston, SC 29425. l%e age-related differenoas in sensitivity of myozudium to the toxic effects of cardiqlycosides are well-lmoWn but reinain irlccqletely m. specific [33]msaswedinisolatedonine cuabainbindingwas ventridar~fmn neonatal (X10 daveofaae1 iandadulthearts. Inadditio?l,them~CXT&XY0fmvocvtes fruneadlwe ~~cieterminedsothatcellsurface~~dbe~cula~~ !lbeaverage& was 3.77xlO-‘5&l in the noon&o (W=8) ard 5.18xlO-‘5cell in the adult (W=l2). ‘Iho spherical. neonam myocytes had an average diameter of 12.02 nta ard tha cyltiical adult myocyks had an average short axis of 36.4-m and lcnqaxis of 148.8 mm\. !lhe The % of laqer (p10.047) than in density of ouabain binding affinity of ouabain binding tich may account for the
p89
POSTNATAL
CARDIAC
in n&mates at-d i0.82-‘7pycari! (Wl5) in the the nmnatal myoqtes (83.5f46.4 nM, W=8) was siqnificzmtiy the adult cells (16.67k18.5 H, W=3). Conclusion: liro sites appears sirrrilar in these two age gnups; huWave.r, the was significantly less in the noonate m in the adult, 1cs-re.r sensitivity to digitalis in the nawhoxn.
DEVELOPMENT
IS ALTERED
BY
CO EXPOSURE
David G. Penney1 and Gary L. Engehnann 2. (1) Dept. of Physiol., Wayne State University, Detroit, MI 48201 and (2) Dem. of Med., Lovola University of Chicago, Maywood, IL 60153 Previous‘smd& suggest that chronic CO exposure fo;seveml weeks post-birth, stimulates myocyte hyperplasia and results in various irreversible myocardial changes. Molecular analysis of the steady state levels of several gene tmnscriots SUDDOIIS a uroliferative and hvnertrophic response in 500 ppm COtreated rat pups. Evidence to s&es; &creased proliferation presumably of the myocyte population, was found in ‘I-dav old CO-hearts based on elevated levels of the FGF-receptor fig. In contrast, the level of expression of IGF-II and the Type-2 IGF receptor were not altered by CO exposure. Expression of myosin heavy chain-beta and atrial natriuretic factor were extended in the CO-hearts beyond the first postnatal week. surrrrestinn the retention of “fetal-like” cardiac properties. Expression of metabolic enzymes (creatine kin& M) and myosin thin filaments (cardiac-troponin C and I> were unaffected by-COtreatment. A signif. increase in the expression of TGF-Bl was seen in 7- and 14&y CO-hearts. This increase may be related to the alterations in capillary am&genesis detected. After 39 days of CO exposure. left ventricular caoillarv densitv was increased lo- 15% above air controls: while right ventricular (RV) capillary density was ~gnificantly increased 35-40% above air controls. .Morphometric analysis also indicated sirmif. cellular hvnertrouhv of the RV mvocvtes in the CO-treated pups. Results from this study indicate that neonatal CG exposuie can modulate the final myocyte cell number of the heart by possible autocrine and/or paracrine mechanisms of action. In addition, cardiac angiogenesis, particularly of the RV, is significantly accentuated by this form of RV hypertrophy under similar regulatory controls.
p90
THE EFFECT OF INCREASED AFTERLOAD TO THE HEART PEPTIDE (ANP) IN THE DEVELOPING SHEEP FETUS Barbara Y. Hargrave & Mickey C. Castle. Depts. of Biological & Pharmacology, Eastern Virginia Medical School, Norfolk,
ON THE SECRETION Sciences, VA. 23539
Old Dominion
OF ATRIAL Univ.
NATRIURETIC and
Physiology
In the adult, ANP regulates renal and cardiovascular function when atrial pressure is increased. To assess the effect of increased afterload to the fetal heart on ANP secretion we studied 6 chronically cannulated fetal We infused phenylephrine (6 ug/min) sheep-3 at 118-1284 (young) and 3 at 130-146d (older) gestation. intravenously for 30 min into all fetuses. Fetal ~0, increased and pC0, decreased in the young fetuses but did not change in the older fetuses. Fetal protein increased 5 min into the infusion and remained elevated throughout the experiment in the young fetuses but did not change significantly in the older fetuses. Fetal mean arterial blood pressure increased 1.7 fold in the young and 1.2 fold in the older fetuses and remained elevated in both groups 5 min after the infusion was stopped. Fetal plasma ANP concentrations increased 8 fold in the young and 3 fold in the older fetuses. Plasma aldosterone concentrations increased in the In addition, fetal bl o od glucose young fetuses but did not change significantly in the older fetuses. concentrations increased in the okfer but did not change in the younger fetuses. These data suggest that the sensitivity to stimuli that increase ANP secretion in the developing fetus may change as a function of gestation.
s.34
III) (1992)
p88ENsrmrANDMFlNITYCFSPECIFICCU?=UNBINLXEINISCIMED~?iNDADuup rBwl!BImm IceMeth W. Hewett, Kylie Wz&in, EYancis G. spinale, Christine E. Williamson, Paul C. Gillette. radical rrniversity of south Carolina, Division of pediatric cardiology, Charleston, SC 29425. l%e age-related differenoas in sensitivity of myozudium to the toxic effects of cardiqlycosides are well-lmoWn but reinain irlccqletely m. specific [33]msaswedinisolatedonine cuabainbindingwas ventridar~fmn neonatal (X10 daveofaae1 iandadulthearts. Inadditio?l,them~CXT&XY0fmvocvtes fruneadlwe ~~cieterminedsothatcellsurface~~dbe~cula~~ !lbeaverage& was 3.77xlO-‘5&l in the noon&o (W=8) ard 5.18xlO-‘5cell in the adult (W=l2). ‘Iho spherical. neonam myocytes had an average diameter of 12.02 nta ard tha cyltiical adult myocyks had an average short axis of 36.4-m and lcnqaxis of 148.8 mm\. !lhe The % of laqer (p10.047) than in density of ouabain binding affinity of ouabain binding tich may account for the
p89
POSTNATAL
CARDIAC
in n&mates at-d i0.82-‘7pycari! (Wl5) in the the nmnatal myoqtes (83.5f46.4 nM, W=8) was siqnificzmtiy the adult cells (16.67k18.5 H, W=3). Conclusion: liro sites appears sirrrilar in these two age gnups; huWave.r, the was significantly less in the noonate m in the adult, 1cs-re.r sensitivity to digitalis in the nawhoxn.
DEVELOPMENT
IS ALTERED
BY
CO EXPOSURE
David G. Penney1 and Gary L. Engehnann 2. (1) Dept. of Physiol., Wayne State University, Detroit, MI 48201 and (2) Dem. of Med., Lovola University of Chicago, Maywood, IL 60153 Previous‘smd& suggest that chronic CO exposure fo;seveml weeks post-birth, stimulates myocyte hyperplasia and results in various irreversible myocardial changes. Molecular analysis of the steady state levels of several gene tmnscriots SUDDOIIS a uroliferative and hvnertrophic response in 500 ppm COtreated rat pups. Evidence to s&es; &creased proliferation presumably of the myocyte population, was found in ‘I-dav old CO-hearts based on elevated levels of the FGF-receptor fig. In contrast, the level of expression of IGF-II and the Type-2 IGF receptor were not altered by CO exposure. Expression of myosin heavy chain-beta and atrial natriuretic factor were extended in the CO-hearts beyond the first postnatal week. surrrrestinn the retention of “fetal-like” cardiac properties. Expression of metabolic enzymes (creatine kin& M) and myosin thin filaments (cardiac-troponin C and I> were unaffected by-COtreatment. A signif. increase in the expression of TGF-Bl was seen in 7- and 14&y CO-hearts. This increase may be related to the alterations in capillary am&genesis detected. After 39 days of CO exposure. left ventricular caoillarv densitv was increased lo- 15% above air controls: while right ventricular (RV) capillary density was ~gnificantly increased 35-40% above air controls. .Morphometric analysis also indicated sirmif. cellular hvnertrouhv of the RV mvocvtes in the CO-treated pups. Results from this study indicate that neonatal CG exposuie can modulate the final myocyte cell number of the heart by possible autocrine and/or paracrine mechanisms of action. In addition, cardiac angiogenesis, particularly of the RV, is significantly accentuated by this form of RV hypertrophy under similar regulatory controls.
p90
THE EFFECT OF INCREASED AFTERLOAD TO THE HEART PEPTIDE (ANP) IN THE DEVELOPING SHEEP FETUS Barbara Y. Hargrave & Mickey C. Castle. Depts. of Biological & Pharmacology, Eastern Virginia Medical School, Norfolk,
ON THE SECRETION Sciences, VA. 23539
Old Dominion
OF ATRIAL Univ.
NATRIURETIC and
Physiology
In the adult, ANP regulates renal and cardiovascular function when atrial pressure is increased. To assess the effect of increased afterload to the fetal heart on ANP secretion we studied 6 chronically cannulated fetal We infused phenylephrine (6 ug/min) sheep-3 at 118-1284 (young) and 3 at 130-146d (older) gestation. intravenously for 30 min into all fetuses. Fetal ~0, increased and pC0, decreased in the young fetuses but did not change in the older fetuses. Fetal protein increased 5 min into the infusion and remained elevated throughout the experiment in the young fetuses but did not change significantly in the older fetuses. Fetal mean arterial blood pressure increased 1.7 fold in the young and 1.2 fold in the older fetuses and remained elevated in both groups 5 min after the infusion was stopped. Fetal plasma ANP concentrations increased 8 fold in the young and 3 fold in the older fetuses. Plasma aldosterone concentrations increased in the In addition, fetal bl o od glucose young fetuses but did not change significantly in the older fetuses. concentrations increased in the okfer but did not change in the younger fetuses. These data suggest that the sensitivity to stimuli that increase ANP secretion in the developing fetus may change as a function of gestation.
s.34