Atrial natriuretic peptide behaviour and myocyte hypertrophic profile in combined pressure and volume-induced cardiac hypertrophy.
OBJECTIVE
To investigate cardiomyocyte hypertrophy and hormonal profile in cardiac hypertrophy resulting from sequentially applied overloads.


METHODS
We studied Sprague-Dawley rats with renovascular hypertension (RV), where pressure overload predominates, or deoxycorticosterone acetate (DOCA)-salt (DS), where volume overload predominates, at 2 and 4 weeks of treatment, and the combination of both models in inverse sequence: RV 2 weeks/DS 2 weeks (RV2/DS2) and DS 2 weeks/RV 2 weeks (DS2/RV2), and their sham controls (Sh).


RESULTS
Blood pressure and cardiomyocyte diameter increased to a similar extent in RV and DS at 2 and 4 weeks and in combined models. Cardiomyocyte length increased remarkably in the DS4 group. Circulating atrial natriuretic peptide (ANP) was elevated in all hypertensive groups after 2 and 4 weeks. The RV2/DS2 group showed similar plasma ANP levels to RV4, but DS2/RV2 exhibited a three-fold increase in ANP levels (P<0.001 versus Sh4, DS2 and DS4). Atrial ANP mRNA remained unchanged in all groups. DS treatment alone or in combination with RV increased left ventricular ANP mRNA, meanwhile only RV treatment increased left ventricular B-type natriuretic peptide (BNP) mRNA. Ventricular ANP expression levels, but not circulating ANP, correlated with both cardiomyocyte diameter (r=0.859, P<0.01) and length (r=0.848, P<0.01). Renal expression of natriuretic peptide receptor C (NPR-C) was unchanged in RV4 but decreased to a similar extent in the DS4 group and both combined treatments.


CONCLUSIONS
Morphometric patterns seem to be more related to the paracrine function of the heart than to the secretion of ANP and the endocrine function. Plasma ANP in the DS2/RV2 group could indicate a different evolution of the remodelling process. ANP expression seems to be a more sensitive marker for volume than for pressure overload.
Cavallero
Susana
S
Departments of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), National Council of Scientific and Technological Research (CONICET), Argentina. susanac@ffyb.uba.ar
González
Germán E
GE
Puyó
Ana M
AM
Rosón
María I
MI
Pérez
Susana
S
Morales
Celina
C
Hertig
Cecilia M
CM
Gelpi
Ricardo J
RJ
Fernández
Belisario E
BE
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology*; D001483:Base Sequence; D001835:Body Weight; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size; D016133:Polymerase Chain Reaction; D011312:Pressure; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D009320:Atrial Natriuretic Factor