A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release

Néstor G. Pérez, María C. Villa-Abrille, Ernesto A. Aiello, Raúl A. Dulce, Horacio E. Cingolani, María C. Camilión De Hurtado

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Objective: This work was aimed to prove that release/formation of endogenous endothelin acting in an autocrine/paracrine fashion contributes to the increase in contractility promoted by a low dose of angiotensin II. Methods: Isolated cat papillary muscles were used for force, pHi, [Na +]i and [Ca2+]i measurements and isolated cat myocytes for patch-clamp experiments. Results: In papillary muscles, 1.0 nmol/l angiotensin II increased force by 23±2% (n=4, P<0.05), [Na+]i by 2.2±0.2 mmol/l (n=4, P<0.05), and peak (but not diastolic) Ca2+ from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, P<0.05), without affecting pH i. Force and [Na+]i increase were abolished by inhibition of the Na+/H+ exchanger (NHE) with the inhibitor HOE642, blockade of endothelin receptors with the nonselective antagonist TAK044 and by inhibition of the endothelin-converting enzyme with phosphoramidon. Force but not [Na+]i increase was abolished by inhibition of reverse Na+/Ca2+ exchange (NCX) with the inhibitor KB-R7943. Similar increase in force (21±2%, n=4, P<0.05) and in [Na+]i (2.4±0.4 mmol/l, n=4, P<0.05) that were also suppressed by TAK044 and HOE642 were induced by exogenous 5.0 nmol/l endothelin-1. KB-R7943 reverted the endothelin-1 effect on force but not on [Na+]i. In isolated myocytes, exogenous endothelin-1 dose-dependently increased the NCX current and shifted the NCX reversal potential (ENCX) to a more negative value (ΔE NCX: -10±3 and -17±5 mV, with 1 and 10 nmol/l endothelin-1, respectively, n=12). The latter effect was prevented by HOE642. Conclusion: Taken together, the results indicate that a low dose of angiotensin II induces release of endothelin, which, in autocrine/paracrine fashion activates the Na+/H+ exchanger, increases [Na +]i and changes ENCX, promoting the influx of Ca2+ that leads to a positive inotropic effect (PIE).

Original languageEnglish (US)
Pages (from-to)589-597
Number of pages9
JournalCardiovascular research
Issue number3
StatePublished - Dec 1 2003
Externally publishedYes


  • Angiotensin
  • Cat papillary muscles
  • E-C coupling
  • Endothelins
  • Ion transport
  • Isolated cat myocytes
  • Na/Ca-exchanger
  • Na/H-exchanger

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release'. Together they form a unique fingerprint.

Cite this