Angiotensin AT2 receptor agonist stimulates high stretch induced- ANP secretion via PI3K/NO/sGC/PKG/pathway |
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| Affiliation: | 1. Division of Oncology, Children''s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;2. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;3. Division of Cardiology, Children''s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;4. Jill and Mark Fishman Center for Lymphatic Disorders, Children''s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;1. Instituto de Fisiopatología Cardiovascular, Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Argentina;2. Instituto de Bioquímica y Medicina Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;1. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Unidad de Neurocríticos, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain;2. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Departamento de Medicina Preventiva y Salud Pública, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain;3. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Departamento de Fisiología Médica y Biofísica, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain |
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| Abstract: | Angiotensin II (Ang II) type 1 receptor (AT1R) mediates the major cardiovascular effects of Ang II. However, the effects mediated via AT2R are still controversial. The aim of the present study is to define the effect of AT2R agonist CGP42112A (CGP) on high stretch-induced ANP secretion and its mechanism using in vitro and in vivo experiments. CGP (0.01, 0.1 and 1 μM) stimulated high stretch-induced ANP secretion and concentration from isolated perfused rat atria. However, atrial contractility and the translocation of extracellular fluid did not change. The augmented effect of CGP (0.1 μM) on high stretch-induced ANP secretion was attenuated by the pretreatment with AT2R antagonist or inhibitor for phosphoinositol 3-kinase (PI3K), nitric oxide (NO), soluble guanylyl cyclase (sGC), or protein kinase G (PKG). However, antagonist for AT1R or Mas receptor did not influence CGP-induced ANP secretion. In vivo study, acute infusion of CGP for 10 min increased plasma ANP level without blood pressure change. In renal hypertensive rat atria, AT2R mRNA and protein levels were up-regulated and the response of plasma ANP level to CGP infusion in renal hypertensive rats augmented. The pretreatment with AT2R antagonist for 10 min followed by CGP infusion attenuated an increased plasma ANP level induced by CGP. However, pretreatment with AT1R or Mas receptor antagonist unaffected CGP-induced increase in plasma ANP level. Therefore, we suggest that AT2R agonist CGP stimulates high stretch-induced ANP secretion through PI3K/NO/sGC/PKG pathway and these effects are augmented in renal hypertensive rats. |
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| Keywords: | Angiotensin Receptor Atrial natriuretic peptide Pressure Hypertension |
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