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In vivo α-adrenergic responses and troponin I phosphorylation: anesthesia interactions
- Source :
- Journal of Applied Physiology. 98:1163-1170
- Publication Year :
- 2005
- Publisher :
- American Physiological Society, 2005.
-
Abstract
- The mechanisms by which α-adrenergic stimulation of the heart in vivo can cause contractile dysfunction are not well understood. We hypothesized that α-adrenergic-mediated contractile dysfunction is mediated through protein kinase C phosphorylation of troponin I, which in in vitro experiments has been shown to reduce actomyosin Mg-ATPase activity. We studied pressure-volume loops in transgenic mice expressing mutant troponin I lacking protein kinase C phosphorylation sites and hypothesized altered responses to phenylephrine. As anesthesia agents can produce markedly different effects on contractility, we studied two agents: avertin and α-chloralose-urethane. With α-chloralose-urethane, at baseline, there were no contractile abnormalities in the troponin I mutants. Phenylephrine produced a 50% reduction in end-systolic elastance in wild-type controls, although a 9% increase in troponin I mutants ( P < 0.05). Avertin was associated with reduced contractility compared with α-chloralose-urethane. Avertin anesthesia, at baseline, produced a reduction in end-systolic elastance by 31% in the troponin I mutants compared with wild-type ( P < 0.05), and this resulted in further marked systolic and diastolic dysfunction with phenylephrine in the troponin I mutants. Dobutamine produced no significant difference in the contractile phenotype of the transgenic mice with either anesthetic regimen. In conclusion, these data (α-chloralose-urethane) demonstrate that α-adrenergic-mediated force reduction is mediated through troponin I protein kinase C phosphorylation. β-Adrenergic responses are not mediated through this pathway. Altering the myofilament force-calcium relationship may result in in vivo increased sensitivity to negative inotropy. Thus choice of a negative inotropic anesthetic agent (avertin) with phenylephrine can lead to profound contractile dysfunction.
- Subjects :
- medicine.medical_specialty
Physiology
Ratón
Mice, Transgenic
Stimulation
Biology
Ventricular Function, Left
Contractility
Mice
In vivo
Physiology (medical)
Internal medicine
Troponin I
medicine
Animals
Phosphorylation
Protein Kinase C
Protein kinase C
Anesthetics
Ethanol
Receptors, Adrenergic, alpha
Myocardial Contraction
Endocrinology
Chloralose
Anesthesia
Circulatory system
Subjects
Details
- ISSN :
- 15221601 and 87507587
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Physiology
- Accession number :
- edsair.doi.dedup.....9848bf043bc9503faeba9a5ab6a47b90
- Full Text :
- https://doi.org/10.1152/japplphysiol.00959.2004