A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release
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<SUP>+<...
| Autores principales: | , , , , , |
|---|---|
| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2003
|
| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/84453 |
| Aporte de: |
| id |
I19-R120-10915-84453 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Angiotensin Cat papillary muscles E-C coupling Endothelins Ion transport Isolated cat myocytes Na/Ca-exchanger Na/H-exchanger |
| spellingShingle |
Ciencias Médicas Angiotensin Cat papillary muscles E-C coupling Endothelins Ion transport Isolated cat myocytes Na/Ca-exchanger Na/H-exchanger Pérez, Néstor Gustavo Villa Abrille, María Celeste Aiello, Ernesto Alejandro Dulce, Raúl Ariel Cingolani, Horacio Eugenio Camilión de Hurtado, María Cristina A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| topic_facet |
Ciencias Médicas Angiotensin Cat papillary muscles E-C coupling Endothelins Ion transport Isolated cat myocytes Na/Ca-exchanger Na/H-exchanger |
| description |
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<SUP>+</SUP>]<SUB>i</SUB> and [Ca<SUP>2+</SUP>]<SUB>i</SUB> 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<SUP>+</SUP>]<SUB>i</SUB> by 2.2±0.2 mmol/l (n=4, P<0.05), and peak (but not diastolic) Ca<SUP>2+</SUP> from 0.674±0.11 to 0.768±0.13 μmol/l (n=4, P<0.05), without affecting pH i. Force and [Na<SUP>+</SUP>]<SUB>i</SUB> increase were abolished by inhibition of the Na<SUP>+</SUP>/H<SUP>+</SUP> 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<SUP>+</SUP>]<SUB>i</SUB> increase was abolished by inhibition of reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchange (NCX) with the inhibitor KB-R7943. Similar increase in force (21±2%, n=4, P<0.05) and in [Na<SUP>+</SUP>]<SUB>i</SUB> (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<SUP>+</SUP>]<SUB>i</SUB>. In isolated myocytes, exogenous endothelin-1 dose-dependently increased the NCX current and shifted the NCX reversal potential (E<SUB>NCX</SUB>) to a more negative value (ΔE<SUB>NCX</SUB>: -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<SUP>+</SUP>/H<SUP>+</SUP> exchanger, increases [Na<SUP>+</SUP>]<SUB>i</SUB> and changes E<SUB>NCX</SUB>, promoting the influx of Ca<SUP>2+</SUP> that leads to a positive inotropic effect (PIE). |
| format |
Articulo Articulo |
| author |
Pérez, Néstor Gustavo Villa Abrille, María Celeste Aiello, Ernesto Alejandro Dulce, Raúl Ariel Cingolani, Horacio Eugenio Camilión de Hurtado, María Cristina |
| author_facet |
Pérez, Néstor Gustavo Villa Abrille, María Celeste Aiello, Ernesto Alejandro Dulce, Raúl Ariel Cingolani, Horacio Eugenio Camilión de Hurtado, María Cristina |
| author_sort |
Pérez, Néstor Gustavo |
| title |
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| title_short |
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| title_full |
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| title_fullStr |
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| title_full_unstemmed |
A low dose of angiotensin II increases inotropism through activation of reverse Na+/Ca2+ exchange by endothelin release |
| title_sort |
low dose of angiotensin ii increases inotropism through activation of reverse na+/ca2+ exchange by endothelin release |
| publishDate |
2003 |
| url |
http://sedici.unlp.edu.ar/handle/10915/84453 |
| work_keys_str_mv |
AT pereznestorgustavo alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT villaabrillemariaceleste alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT aielloernestoalejandro alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT dulceraulariel alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT cingolanihoracioeugenio alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT camiliondehurtadomariacristina alowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT pereznestorgustavo lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT villaabrillemariaceleste lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT aielloernestoalejandro lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT dulceraulariel lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT cingolanihoracioeugenio lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease AT camiliondehurtadomariacristina lowdoseofangiotensiniiincreasesinotropismthroughactivationofreversenaca2exchangebyendothelinrelease |
| bdutipo_str |
Repositorios |
| _version_ |
1764820488752726019 |