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

• Type: Article in International Scientific Journal
• Date: 2006

Authors

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

Journal

Title: British Journal of Pharmacology

Vol. 147 No. 6

Pages: 690-697

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 23 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8