Investigation of the cardiomyocyte dysfunction in bradykinin type 2 receptor knockout mice.
OBJECTIVE
Bradykinin type 2 receptor (B(2)R) is the key component to trigger the intracellular signaling pathway in response to bradykinin under physiological conditions. The present study sought to investigate whether the B(2)R gene deletion will have an impact on myocardial function.


METHODS
Isolated cell shortening, patch-clamp technique, Western blot and confocal microscopy.


RESULTS
Isolated cell shortening measurements showed significant reduction in B(2)R knockout (B(2)R(-/-)) left ventricular cardiac myocytes' shortening. Whole-cell recordings were used to study the electrophysiological aspects of the left ventricular B(2)R(-/-) cardiomyocytes. Results showed: 1) action potential lengthening; 2) unchanged inwardly rectifying K(+) current; 3) reduced transient outward K(+) (I(to)) and L-type Ca(2+) current densities; 5) changes in kinetic properties related to I(to) and I(Ca,L). In addition, transient sarcoplasmic reticulum (SR) Ca(2+) release was found to be smaller in B(2)R(-/-) cardiomyocytes. Importantly, evidence is provided that NO constitutive production is, at least in part, responsible for the reported electrophysiological modifications observed in cardiomyocytes from B(2)R(-/-) mice. Surprisingly, NO is not involved in the SR Ca(2+) release reduction as demonstrated in the present study.


CONCLUSIONS
Taken together, our findings indicate that B(2)R plays a fundamental role in the regulation of cardiac function and Ca(2+) homeostasis, probably through a NO dependent pathway. These results may contribute to our understanding of the kinins participation in the control of cardiac function.
Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Danilo
D
Roman-Campos
Hugo Leonardo
HL
Duarte
Enéas Ricardo
ER
Gomes
Carlos Henrique
CH
Castro
Silvia
S
Guatimosim
Antonio José
AJ
Natali
Alvair Pinto
AP
Almeida
João Bosco
JB
Pesquero
Jorge Luiz
JL
Pesquero
Jader Santos
JS
Cruz
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D017353:Gene Deletion; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D002118:Calcium