Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

Bart Fj Heijnen, Leonie Pj Pelkmans, Ah Jan Danser, Ingrid M Garrelds, John J Mullins, Jo Gr De Mey, Harry Aj Struijker-Boudier, Ben Ja Janssen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.
OriginalsprogEngelsk
TidsskriftJournal of the Renin-Angiotensin-Aldosterone System
ISSN1470-3203
DOI
StatusUdgivet - 5. mar. 2013

Fingeraftryk

Renin-Angiotensin System
Renin
Heart Ventricles
Young Adult

Bibliografisk note

Published online before print

Citer dette

Heijnen, Bart Fj ; Pelkmans, Leonie Pj ; Danser, Ah Jan ; Garrelds, Ingrid M ; Mullins, John J ; De Mey, Jo Gr ; Struijker-Boudier, Harry Aj ; Janssen, Ben Ja. / Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats. I: Journal of the Renin-Angiotensin-Aldosterone System. 2013.
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abstract = "This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.",
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Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats. / Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan; Garrelds, Ingrid M; Mullins, John J; De Mey, Jo Gr; Struijker-Boudier, Harry Aj; Janssen, Ben Ja.

I: Journal of the Renin-Angiotensin-Aldosterone System, 05.03.2013.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

AU - Heijnen, Bart Fj

AU - Pelkmans, Leonie Pj

AU - Danser, Ah Jan

AU - Garrelds, Ingrid M

AU - Mullins, John J

AU - De Mey, Jo Gr

AU - Struijker-Boudier, Harry Aj

AU - Janssen, Ben Ja

N1 - Published online before print

PY - 2013/3/5

Y1 - 2013/3/5

N2 - This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.

AB - This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.

U2 - 10.1177/1470320313480537

DO - 10.1177/1470320313480537

M3 - Journal article

C2 - 23462119

JO - Journal of the Renin-Angiotensin-Aldosterone System

JF - Journal of the Renin-Angiotensin-Aldosterone System

SN - 1470-3203

ER -