Etude comparative de la fonction cardiaque chez le rat transgenique hypertendu, chez le rat spontanement hypertendu et chez le rat normotendu [A comparative study of cardiac function in transgenic hypertensive rats, in spontaneously hypertensive rats and in normotensive rats]

Item Type:	Article
Title:	Etude comparative de la fonction cardiaque chez le rat transgenique hypertendu, chez le rat spontanement hypertendu et chez le rat normotendu [A comparative study of cardiac function in transgenic hypertensive rats, in spontaneously hypertensive rats and in normotensive rats]
Creators Name:	Bohlender, J. and Hildenbrand, U. and Schlegel, W.P. and Hempel, P. and Nissen, E. and Krause, E.G. and Bartel, S.
Abstract:	Left ventricular hypertrophy (LVH) entails numerous functional and molecular changes that ultimately lead to cardiac insufficiency. The renin-angiotensin system and adrenergic receptor signalling pathway have both been implicated in LVH progression and interactions between these factors may precipitate contractile dysfunction. We therefore investigated cardiac function in hypertensive rats transgenic for the human renin and angiotensinogen genes (TGR) having a genetic activation of the renin-angiotensin system, stroke-prone spontaneously hypertensive rats (SHR) and normotensive controls (CTR) aged 6 weeks. The isolated perfused heart model was used and the effect of isoproterenol (0.1-1000 nmol/L on cardiac function was studied. Cardiac protein and gene expression was studied by Western blot and RNase protection assay. TGR had 75 mmHg higher blood pressure and a 24% higher cardiac/body weight ratio than CTR; blood pressure in SHR was 17 mmHg higher without heart wheight difference (p<0.05). Basal Pmax, +dP/dt and -dP/dt were higher in TGR and SHR compared with CTR hearts. Isoproterenol stimulated these parameters by a maximum factor 6-8 in CTR and SHR but had almost no effect in TGR (p<0.05). Basal CF per g heart weight was similar in all experimental groups. Isoproterenol produced a significantly smaller vasodilation in TGR compared with CTR or SHR. β1 and β2 receptor and Gsα proteins were similar in TGR, SHR and CTR. Giα was increased in TGR hearts (p<0.05). Converting enzyme and atrial natriuretic factor mRNA expression was increased (p<0.01) while β1 receptor, adenylyl-cyclase V, SERCA2a and phospholamban mRNA expression was unchanged in TGR compared with CTR. Thus, LVH in TGR is characterised by early adrenergic dysfunction and β1 receptor signalling abnormalities indicating progressive functional deterioration. The data may serve as support for an early preventive intervention in angiotensin-II dependent cardiac hypertrophy and may have also implications for patients with genetic alterations of the renin-angiotensin system.
Keywords:	Adrenergic Beta-Agonists, Angiotensinogen, Atrial Natriuretic Factor, Beta Adrenergic Receptors, Blood Pressure, Body Weight, Cardiotonic Agents, Gene Expression Regulation, Genetically Modified Animals, Gi-Go GTP-Binding Protein Alpha Subunits, Gs GTP-Binding Protein alpha Subunits, Heart, Hypertension, Inbred SHR Rats, Isoproterenol, Left Ventricular Hypertrophy, Myocardial Contraction, Organ Size, Peptidyl-Dipeptidase A, Renin, Renin-Angiotensin System, Serine Proteinase Inhibitors, Sprague-Dawley Rats, Vasodilator Agents, Western Blotting, Animals, Rats
Source:	Archives des Maladies du Coeur et des Vaisseaux
ISSN:	0003-9683
Publisher:	JB Ballierere
Volume:	93
Number:	8
Page Range:	993-996
Date:	1 August 2000
PubMed:	View item in PubMed

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