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Title: Kinin B-1 receptor participates in the control of cardiac function in mice
Authors: Lauton-Santos, Sandra
Guatimosim, Silvia
Castro, Carlos H.
Oliveira, Fernando A.
Almeida, Alvair P.
Dias-Peixoto, Marco Fabricio
Gomes, Maria Aparecida
Pessoa, Phillipe
Pesquero, Jorge L.
Pesquero, Joao B.
Bader, Michael
Cruz, Jader S.
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med
Keywords: kinins
nitric oxide
B-1 receptor
cardiac myocytes
Confocal microscopy
Issue Date: 16-Aug-2007
Publisher: Elsevier B.V.
Citation: Life Sciences. Oxford: Pergamon-Elsevier B.V., v. 81, n. 10, p. 814-822, 2007.
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 13, receptors. However, the physiological relevance of B 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 Ca2+ 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 Ca2+ current (I-Ca,I-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 Ca2+ transient (3.1 +/- 0.06 vs. 3.4 +/- 0.09 for B and WT, respectively). There was an increase in I-Ca,I-L at depolarized membrane potentials. Interestingly, the inactivation kinetics of I-Ca,I-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. (c) 2007 Elsevier Inc. All rights reserved.
ISSN: 0024-3205
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