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Kinin B1 receptor participates in the control of cardiac function in mice

Item Type:Article
Title:Kinin B1 receptor participates in the control of cardiac function in mice
Creators Name:Lauton-Santos, S. and Guatimosim, S. and Castro, C.H. and Oliveira, F.A. and Almeida, A.P. and Dias-Peixoto, M.F. and Gomes, M.A. and Pessoa, P. and Pesquero, J.L. and Pesquero, J.B. and Bader, M. and Cruz, J.S.
Abstract:The kinins have an important role in control of the cardiovascular system. They have been associated with protective effects in the heart tissue. Kinins act through stimulation of two 7-transmembrane G protein-coupled receptors, denoted B(1) and B(2) receptors. However, the physiological relevance of B(1) receptor in the heart has not been clearly established. Using B(1) kinin receptor gene knock-out mice we tested the hypothesis that the B(1) receptor plays an important role in the control of baseline cardiac function. We examined the functional aspects of the intact heart and also in the isolated cardiomyocytes to study intracellular Ca(2+) cycling by using confocal microscopy and whole-cell voltage clamp techniques. We measured heart rate, diastolic and systolic tension, contraction and relaxation rates and, coronary perfusion pressure. Whole-cell voltage clamp was performed to measure L-type Ca(2+) current (I(Ca,L)). The hearts from B(1)(-/-) mice showed smaller systolic tension. The average values for WT and B(1)(-/-) mice were 2.6+/-0.04 g vs. 1.6+/-0.08 g, respectively. This result can be explained, at least in part, by the decrease in the Ca(2+) transient (3.1+/-0.06 vs. 3.4+/-0.09 for B(1)(-/-) and WT, respectively). There was an increase in I(Ca,L) at depolarized membrane potentials. Interestingly, the inactivation kinetics of I(Ca,L) was statistically different between the groups. The coronary perfusion pressure was higher in the hearts from B(1)(-/-) mice indicating an increase in coronary resistance. This result can be explained by the significant reduction of eNOS (NOS-3) expression in the aorta of B(1)(-/-) mice. Collectively, our results demonstrate that B(1) receptor exerts a fundamental role in the mammalian cardiac function.
Keywords:Kinins, Nitric Oxide, B1 Receptor, Cardiac Myocytes, Patch-Clamp, Confocal Microscopy, Animals, Mice
Source:Life Sciences
Publisher:Elsevier (The Netherlands)
Page Range:814-822
Date:16 August 2007
Official Publication:https://doi.org/10.1016/j.lfs.2007.06.033
PubMed:View item in PubMed

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