Effects of long-term, high-altitude hypoxia on tension and intracellular calcium responses in coronary arteries of fetal and adult sheep.
J Soc Gynecol Investig
; 13(1): 11-8, 2006 Jan.
Article
en En
| MEDLINE
| ID: mdl-16303320
ABSTRACT
OBJECTIVES:
We have previously shown that after exposure to long-term hypoxia, fetal coronary flow is maintained at control levels despite a 25% reduction in cardiac output. We also demonstrated that coronary vascular rings isolated from the long-term hypoxic fetuses and studied in well-oxygenated bath system displayed significantly reduced depolarization-induced contraction strength in response to KCl. To study the mechanism of reduced fetal coronary vascular responses to KCl-induced contractions following exposure to long-term hypoxia, we measured tension and intracellular calcium simultaneously, as well as L-type Ca2+ channel density and sensitivity.METHODS:
Pregnant ewes were housed at altitude (3820 m) for approximately 110 days. At 138 to 141 days of gestation, long-term hypoxic and control animals were killed and fetal and adult left anterior descending coronary artery (LAD) was isolated and studied in a well-oxygenated bath system. Tension and intracellular calcium ([Ca2+]i) were measured simultaneously in response to increasing concentrations of KCl and, in addition, the sensitivity to the calcium channel blocker nifedipine was measured at a half maximal concentration of KCl. We also measured L-type Ca2+ channel density with (+)-[3H]PN200-110.RESULTS:
L-type Ca2+ channel density was decreased by approximately 31% in the long-term hypoxic fetal, but not adult, LAD. Tension in the long-term hypoxic fetal and adult LAD was significantly lower at all concentrations of KCl. [Ca2+]i was lower at rest in both fetal and adult LAD from long-term hypoxic animals and increased to lower levels at all concentrations of KCl. The ratio of tension to [Ca2+]i was also lower at all concentrations of KCl. Sensitivity to nifedipine was unchanged.CONCLUSIONS:
The reduced L-type Ca2+ channel density and the reduced [Ca2+]i response to KCl, as well as the reduced tension response to [Ca2+]i, could potentially be involved in the reduction in depolarization-induced contractions in LAD from long-term hypoxic fetuses. In hypoxic adults, reduced [Ca2+]i and reduced tension response to [Ca2+]i may be involved in the lower tension response to KCl-induced contractions.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Vasos Coronarios
/
Hipoxia Fetal
Límite:
Animals
Idioma:
En
Revista:
J Soc Gynecol Investig
Asunto de la revista:
GINECOLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA