Document Detail


Effects of adrenergic and muscarinic agonist stimulation on IP3 and cyclic nucleotide levels in the pressure overloaded rat heart.
MedLine Citation:
PMID:  9397489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, the dynamic interrelationships between myocardial functional state and changes in the second messenger content in pressure-overloaded hypertrophied hearts were investigated. Forty-three rat hearts were used after partial clamping of the abdominal aorta. The isolated hearts were perfused with Krebs-Henseleit buffer and allocated to perfusion for 20 s or 40 min as controls (n = 12); or with noradrenaline (10(-6) mol l-1, n = 11); carbachol (3 x 10(-7) mol l-1, n = 9); or noradrenaline plus carbachol (10(-6) mol l-1 + 3 x 10(-7) mol l-1, respectively, n = 11). maxdP/dt increased more than 2-fold already after 20 s on noradrenaline stimulation, followed by a significant increase in cAMP. After 40 min, maxdP/dt was lower than the maximal value, although higher than controls. cAMP was also decreased, but still significantly higher than controls. Perfusion with noradrenaline plus carbachol produced the same changes in maxdP/dt as those seen after noradrenaline stimulation alone, but failed to increase cAMP content after both 20 s and 40 min. The inositol trisphosphate (IP3) content was increased 40 min of control perfusion (p < 0.05). Noradrenaline and carbachol, separately, produced an increase in IP3 content already after 20 s (p < 0.05). The combination of noradrenaline plus carbachol also produced an increase of IP3 (p < 0.05; compared to controls), but to a lesser extent when compared either to noradrenaline or carbachol (p < 0.05). After 40 min of perfusion, IP3 was in the same range regardless of added agonist(s) and still slightly above control level (p < 0.05). The early increase in maxdP/dt induced by noradrenaline or the combination of noradrenaline plus carbachol was not paralleled by a decrease in ATP content. This was also the case upon addition of carbachol alone. However, after 40 min of agonistic perfusion, ATP levels were substantially decreased. In conclusion, myocardial IP3 content in pressure-overloaded hypertrophied hearts was not different from that of sham-operated hearts. After agonistic stimulation, an early increase in IP3 formation was seen. Attenuation of the IP3 response by combined stimulation with noradrenaline and carbachol was initially present in pressure-overloaded hypertrophied hearts. After 40 min no attenuation was found for either IP3 or for cAMP content, suggestive of induction of a desensitization.
Authors:
H J Martinussen; A Waldenström; G Ronquist
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of clinical and laboratory investigation     Volume:  57     ISSN:  0036-5513     ISO Abbreviation:  Scand. J. Clin. Lab. Invest.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-01-02     Completed Date:  1998-01-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0404375     Medline TA:  Scand J Clin Lab Invest     Country:  NORWAY    
Other Details:
Languages:  eng     Pagination:  587-94     Citation Subset:  IM    
Affiliation:
Department of Anaesthesiology, University Hospital, Uppsala, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Agonists / pharmacology*
Animals
Aorta, Thoracic / surgery
Cyclic AMP / metabolism*
Cyclic GMP / metabolism
Disease Models, Animal
Hypertrophy, Left Ventricular / drug therapy,  metabolism*
Inositol 1,4,5-Trisphosphate / metabolism*
Ligation
Male
Muscarinic Agonists / pharmacology*
Myocardium / metabolism
Rats
Rats, Sprague-Dawley
Second Messenger Systems / physiology
Ventricular Pressure
Chemical
Reg. No./Substance:
0/Adrenergic Agonists; 0/Muscarinic Agonists; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 85166-31-0/Inositol 1,4,5-Trisphosphate

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