Role of angiotensin II AT1 and AT2 subtype receptors in the regulation of atrial natriuretic peptide expression in salt-restricted rats

Bruna Gigante, Ornella Piras, Carmine Savoia, Paola De Paolis, Speranza Rubattu, Gaia Panina, Massimo Volpe

Research output: Contribution to journalArticle

Abstract

Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. In order to explore the contribution of angiotensin II AT1 (AT1r) and AT2 (AT2r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague-Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low salt regimen and randomly assigned to the following treatment groups: AT1r-blockade (losartan) (10 mg/kg/day) (n = 18), AT2r-blockade (PD123319) (50 μg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT1r-blockade group were subdivided in to two groups: AT1r/AT2r-blockade (losartan+PD123319) (n = 6) and AT1r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT1r-blockade (p <0.001), while it was not affected by AT2r-blockade. Concomitant treatment with both antagonists (AT1r/AT2r-blockade) restored blood pressure values to baseline (p <0.001 vs. AT1r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT1r-blockade (-42 %, p <0.05) and did not change during AT2r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 % and -36 % vs Control and AT1r-blockade, respectively, both p <0.05). ANP expression in ventricles was not affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II receptor subtypes AT1r and AT2r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalBasic Research in Cardiology
Volume95
Issue number1
DOIs
Publication statusPublished - Feb 2000

Fingerprint

Atrial Natriuretic Factor
Angiotensin II
Salts
Losartan
Blood Pressure
Messenger RNA
Atrial Natriuretic Factor Receptors
Angiotensin Receptors
Sprague Dawley Rats
Theoretical Models
Hemodynamics

Keywords

  • Angiotensin II receptors
  • ANP
  • Heart
  • Losartan
  • PD123319

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Role of angiotensin II AT1 and AT2 subtype receptors in the regulation of atrial natriuretic peptide expression in salt-restricted rats. / Gigante, Bruna; Piras, Ornella; Savoia, Carmine; De Paolis, Paola; Rubattu, Speranza; Panina, Gaia; Volpe, Massimo.

In: Basic Research in Cardiology, Vol. 95, No. 1, 02.2000, p. 64-69.

Research output: Contribution to journalArticle

@article{2412d393f2e14f169df8559e67afe86f,
title = "Role of angiotensin II AT1 and AT2 subtype receptors in the regulation of atrial natriuretic peptide expression in salt-restricted rats",
abstract = "Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. In order to explore the contribution of angiotensin II AT1 (AT1r) and AT2 (AT2r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague-Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low salt regimen and randomly assigned to the following treatment groups: AT1r-blockade (losartan) (10 mg/kg/day) (n = 18), AT2r-blockade (PD123319) (50 μg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT1r-blockade group were subdivided in to two groups: AT1r/AT2r-blockade (losartan+PD123319) (n = 6) and AT1r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT1r-blockade (p <0.001), while it was not affected by AT2r-blockade. Concomitant treatment with both antagonists (AT1r/AT2r-blockade) restored blood pressure values to baseline (p <0.001 vs. AT1r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT1r-blockade (-42 {\%}, p <0.05) and did not change during AT2r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 {\%} and -36 {\%} vs Control and AT1r-blockade, respectively, both p <0.05). ANP expression in ventricles was not affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II receptor subtypes AT1r and AT2r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.",
keywords = "Angiotensin II receptors, ANP, Heart, Losartan, PD123319",
author = "Bruna Gigante and Ornella Piras and Carmine Savoia and {De Paolis}, Paola and Speranza Rubattu and Gaia Panina and Massimo Volpe",
year = "2000",
month = "2",
doi = "10.1007/s003950050009",
language = "English",
volume = "95",
pages = "64--69",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "1",

}

TY - JOUR

T1 - Role of angiotensin II AT1 and AT2 subtype receptors in the regulation of atrial natriuretic peptide expression in salt-restricted rats

AU - Gigante, Bruna

AU - Piras, Ornella

AU - Savoia, Carmine

AU - De Paolis, Paola

AU - Rubattu, Speranza

AU - Panina, Gaia

AU - Volpe, Massimo

PY - 2000/2

Y1 - 2000/2

N2 - Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. In order to explore the contribution of angiotensin II AT1 (AT1r) and AT2 (AT2r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague-Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low salt regimen and randomly assigned to the following treatment groups: AT1r-blockade (losartan) (10 mg/kg/day) (n = 18), AT2r-blockade (PD123319) (50 μg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT1r-blockade group were subdivided in to two groups: AT1r/AT2r-blockade (losartan+PD123319) (n = 6) and AT1r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT1r-blockade (p <0.001), while it was not affected by AT2r-blockade. Concomitant treatment with both antagonists (AT1r/AT2r-blockade) restored blood pressure values to baseline (p <0.001 vs. AT1r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT1r-blockade (-42 %, p <0.05) and did not change during AT2r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 % and -36 % vs Control and AT1r-blockade, respectively, both p <0.05). ANP expression in ventricles was not affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II receptor subtypes AT1r and AT2r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.

AB - Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. In order to explore the contribution of angiotensin II AT1 (AT1r) and AT2 (AT2r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague-Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low salt regimen and randomly assigned to the following treatment groups: AT1r-blockade (losartan) (10 mg/kg/day) (n = 18), AT2r-blockade (PD123319) (50 μg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT1r-blockade group were subdivided in to two groups: AT1r/AT2r-blockade (losartan+PD123319) (n = 6) and AT1r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT1r-blockade (p <0.001), while it was not affected by AT2r-blockade. Concomitant treatment with both antagonists (AT1r/AT2r-blockade) restored blood pressure values to baseline (p <0.001 vs. AT1r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT1r-blockade (-42 %, p <0.05) and did not change during AT2r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 % and -36 % vs Control and AT1r-blockade, respectively, both p <0.05). ANP expression in ventricles was not affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II receptor subtypes AT1r and AT2r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.

KW - Angiotensin II receptors

KW - ANP

KW - Heart

KW - Losartan

KW - PD123319

UR - http://www.scopus.com/inward/record.url?scp=0034101280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034101280&partnerID=8YFLogxK

U2 - 10.1007/s003950050009

DO - 10.1007/s003950050009

M3 - Article

C2 - 10752547

AN - SCOPUS:0034101280

VL - 95

SP - 64

EP - 69

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 1

ER -