Document Detail

Gene Deletion of P2Y4 Receptor Lowers Exercise Capacity and Reduces Myocardial Hypertrophy with Swimming Exercise.
MedLine Citation:
PMID:  22865387     Owner:  NLM     Status:  Publisher    
Objective Nucleotides released within the heart under pathological conditions can be involved in cardioprotection or cardiac fibrosis through the activation P2Y(2) and P2Y(6) receptors, respectively. We demonstrated previously that adult P2Y(4)-null mice display a microcardia phenotype related to a cardiac angiogenic defect. To evaluate the functional consequences of this defect, we performed here a combination of cardiac monitoring and exercise tests. Methods We investigated the exercise capacity of P2Y(4) wild type and P2Y(4)-null mice in forced swimming and running tests. Analysis of their stress, locomotion and resignation was realized in open field, black and white box and tail suspension experiments. Exercise-induced cardiac hypertrophy was evaluated after repeated and prolonged exercise in P2Y(4) wild type and P2Y(4)-null hearts. Results We showed that P2Y(4)-null mice have a lower exercise capacity in both swimming and treadmill tests. This was not related to decreased motivation or increased stress, since open field, white and black box and mouse tail suspension tests gave comparable results in P2Y(4) wild type and P2Y(4)-null mice. Heart rate and blood pressure rose normally in P2Y(4)-null swimming mice equipped with a telemetric implant. On the contrary, we observed a delayed recovery of post-exercise blood pressure after exercise in P2Y(4)-null mice. The heart rate increment in response to catecholamines was also similar in P2Y(4) wild type and P2Y(4)-null implanted mice, which is consistent with a similar level of cardiac β receptor expression. Interestingly, the heart of P2Y(4)-null mice displayed a reduced sympathetic innervation associated with a decreased norepinephrine level. We also demonstrated that exercise-induced cardiac hypertrophy was lower in P2Y(4)-null mice after repeated and prolonged exercise. This was associated with a lower increase in cardiomyocyte size and microvessel density. Conclusion Besides its role in cardiac development, P2Y(4) receptor could constitute an important regulator of acute and chronic response to exercise.
Michael Horckmans; Elvira Léon-Gomez; Bernard Robaye; Jean-Luc Balligand; Jean-Marie Boeynaems; Chantal Dessy; Didier Communi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-3
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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