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 journalArticle

Abstract

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+]i by 2.2±0.2 mmol/l (n=4, P2+ from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, Pi. 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+]i (2.4±0.4 mmol/l, n=4, P+]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
Volume60
Issue number3
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Endothelins
Muscle Contraction
Angiotensin II
Sodium-Hydrogen Antiporter
Papillary Muscles
Endothelin-1
Muscle Cells
Cats
Endothelin Receptors
cariporide

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pérez, N. G., Villa-Abrille, M. C., Aiello, E. A., Dulce, R. A., Cingolani, H. E., & Camilión De Hurtado, M. C. (2003). A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release. Cardiovascular Research, 60(3), 589-597. https://doi.org/10.1016/j.cardiores.2003.09.004

A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release. / Pérez, Néstor G.; Villa-Abrille, María C.; Aiello, Ernesto A.; Dulce, Raúl A.; Cingolani, Horacio E.; Camilión De Hurtado, María C.

In: Cardiovascular Research, Vol. 60, No. 3, 01.12.2003, p. 589-597.

Research output: Contribution to journalArticle

Pérez, NG, Villa-Abrille, MC, Aiello, EA, Dulce, RA, Cingolani, HE & Camilión De Hurtado, MC 2003, 'A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release', Cardiovascular Research, vol. 60, no. 3, pp. 589-597. https://doi.org/10.1016/j.cardiores.2003.09.004
Pérez, Néstor G. ; Villa-Abrille, María C. ; Aiello, Ernesto A. ; Dulce, Raúl A. ; Cingolani, Horacio E. ; Camilión De Hurtado, María C. / A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release. In: Cardiovascular Research. 2003 ; Vol. 60, No. 3. pp. 589-597.
@article{e717e5dcc7f249afbbe9bdcec5e78cc9,
title = "A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release",
abstract = "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+]i by 2.2±0.2 mmol/l (n=4, P2+ from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, Pi. 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+]i (2.4±0.4 mmol/l, n=4, P+]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).",
keywords = "Angiotensin, Cat papillary muscles, E-C coupling, Endothelins, Ion transport, Isolated cat myocytes, Na/Ca-exchanger, Na/H-exchanger",
author = "P{\'e}rez, {N{\'e}stor G.} and Villa-Abrille, {Mar{\'i}a C.} and Aiello, {Ernesto A.} and Dulce, {Ra{\'u}l A.} and Cingolani, {Horacio E.} and {Camili{\'o}n De Hurtado}, {Mar{\'i}a C.}",
year = "2003",
month = "12",
day = "1",
doi = "10.1016/j.cardiores.2003.09.004",
language = "English (US)",
volume = "60",
pages = "589--597",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release

AU - Pérez, Néstor G.

AU - Villa-Abrille, María C.

AU - Aiello, Ernesto A.

AU - Dulce, Raúl A.

AU - Cingolani, Horacio E.

AU - Camilión De Hurtado, María C.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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+]i by 2.2±0.2 mmol/l (n=4, P2+ from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, Pi. 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+]i (2.4±0.4 mmol/l, n=4, P+]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).

AB - 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+]i by 2.2±0.2 mmol/l (n=4, P2+ from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, Pi. 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+]i (2.4±0.4 mmol/l, n=4, P+]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).

KW - Angiotensin

KW - Cat papillary muscles

KW - E-C coupling

KW - Endothelins

KW - Ion transport

KW - Isolated cat myocytes

KW - Na/Ca-exchanger

KW - Na/H-exchanger

UR - http://www.scopus.com/inward/record.url?scp=0344196795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344196795&partnerID=8YFLogxK

U2 - 10.1016/j.cardiores.2003.09.004

DO - 10.1016/j.cardiores.2003.09.004

M3 - Article

C2 - 14659804

AN - SCOPUS:0344196795

VL - 60

SP - 589

EP - 597

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -