Angiotensin II acutely decreases myocardial stiffness: a novel AT1, PKC and Na+/H+ exchanger-mediated

• Tipo: Artigo em Revista Científica Internacional
• Data: 2006

Autores

Leite-Moreira AF (Autor) FMUP; Castro-Chaves P (Autor) FMUP; Pimentel-Nunes P (Autor) FMUP; Lima-Carneiro A (Autor) Outra; Guerra MS (Autor) Outra; Soares JB (Autor) FMUP; Ferreira-Martins J (Autor) Outra

Revista

Título: British Journal of Pharmacology

Vol. 147 Nº 6

Páginas: 690-697

ISSN: 0007-1188

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 22 Citações

Scopus - 23 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: P-004-MW9

DOI: 10.1038/sj.bjp.0706659

Abstract (EN): 1 Acute effects of angiotensin II (AngII) on diastolic properties of the myocardium were investigated. 2 Increasing concentrations of AngII (10(-9) to 10(-5) M) were added to rabbit papillary muscles in the absence (n = 11) or presence of: ( i) AT1 receptor antagonists, losartan (10(-6) M; n = 7) or ZD-7155 (10(-7) M; n = 8); (ii) ZD-7155 ( 10(-7) M) plus AT2 receptor antagonist PD-123,319(2 x 10(-6) M; n = 6); (iii) PKC inhibitor, chelerythrine (10(-5) M; n = 8); or (iv) Na+/ H+ exchanger (NHE) inhibitor, 5-(N-methyl-N- isobutyl)-amiloride (10(-6) M; n = 10). Passive length - tension relations were constructed before and after a single concentration of AngII (10(-5) M, n = 6). Effects of AngII infusion (10 mu g kg(-1) min(-1)) were evaluated in in situ rabbit hearts. 3 AngII concentration dependently increased inotropy and resting muscle length (RL). At 10(-5) M, active tension increased 43.3 +/- 6.25% and RL 1.96 +/- 0.4%. Correcting RL to its initial value resulted in a 46 +/- 4% decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the right and downward shift of the passive length - tension relation promoted by AngII. In the intact heart, at matched systolic pressures of 112 mmHg, AngII decreased end-diastolic pressures from 10.3 +/- 0.3 to 5.9 +/- 0.5 mmHg, and minimal diastolic pressures from 8.4 +/- 0.5 to 4.6 +/- 0.6 mmHg. 4 AT1 blockade inhibited AngII effects on myocardial inotropy and stiffness, while PKC or NHE inhibition only significantly attenuated its effects on resting length and tension. 5 In conclusion, AngII decreases myocardial stiffness, an effect that requires AT1 receptor activation and is mediated by PKC and NHE. This represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that AngII is a powerful regulator of cardiac filling.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8