These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Critical role of the chymase/angiotensin-(1-12) axis in modulating cardiomyocyte contractility.
    Author: Li T, Zhang X, Cheng HJ, Zhang Z, Ahmad S, Varagic J, Li W, Cheng CP, Ferrario CM.
    Journal: Int J Cardiol; 2018 Aug 01; 264():137-144. PubMed ID: 29685688.
    Abstract:
    BACKGROUND: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for angiotensin II (Ang II) cardiac activity. The direct contractile effects of Ang-(1-12) in normal and heart failure (HF) remain to be demonstrated. We assessed the hypothesis that Ang-(1-12) may modulate [Ca2+]i regulation and alter cardiomyocyte contractility in normal and HF rats. METHODS AND RESULTS: We compared left ventricle (LV) myocyte contractile and calcium transient ([Ca2+]iT) responses to angiotensin peptides in 16 SD rats with isoproterenol-induced HF and 16 age-matched controls. In normal myocytes, versus baseline, Ang II (10-6 M) superfusion significantly increased myocyte contractility (dL/dtmax: 40%) and [Ca2+]iT (29%). Ang-(1-12) (4 × 10-6 M) caused similar increases in dL/dtmax (34%) and [Ca2+]iT (25%). Compared with normal myocytes, superfusion of Ang II and Ang-(1-12) in myocytes obtained from rats with isoproterenol-induced HF caused similar but significantly attenuated positive inotropic actions with about 42% to 50% less increases in dL/dtmax and [Ca2+]iT. Chymostatin abolished Ang-(1-12)-mediated effects in normal and HF myocytes. The presence of an inhibitory cAMP analog, Rp-cAMPS prevented Ang-(1-12)-induced inotropic effects in both normal and HF myocytes. Incubation of HF myocytes with pertussis toxin (PTX) further augmented Ang II-mediated contractility. CONCLUSIONS: Ang-(1-12) stimulates cardiomyocyte contractile function and [Ca2+]iT in both normal and HF rats through a chymase mediated action. Altered inotropic responses to Ang-(1-12) and Ang II in HF myocytes are mediated through a cAMP-dependent mechanism that is coupled to both stimulatory G and inhibitory PTX-sensitive G proteins.
    [Abstract] [Full Text] [Related] [New Search]