Imbalanced
matrix metalloproteinase (
MMP) activity is involved in hypertensive
cardiac hypertrophy. Pharmacological inhibition of
nuclear factor kappaB (NF-кB) with
pyrrolidine dithiocarbamate (
PDTC) can prevent
MMP up-regulation. We suggested that treatment with
PDTC could prevent 2-kidney, 1-clip (2K1C)
hypertension-induced left ventricular remodelling.
Sham-operated controls or 2K1C rats with
hypertension received either vehicle or
PDTC (100 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure was monitored every week. Histological assessment of left ventricles was carried out with haematoxylin/
eosin sections, and
fibrosis was quantified in
picrosirius red-stained sections. Oxidative stress was evaluated in heart samples with the
dihydroethidium probe. Cardiac
MMP activity was determined by in situ zymography, and cardiac MMP-2 was assessed by immunofluorescence. 2K1C surgery significantly increased systolic blood pressure in the 2K1C vehicle.
PDTC exerted
antihypertensive effects after 2 weeks of treatment. Histology revealed increased left ventricular and septum wall thickness associated with augmented myocyte diameter in hypertensive rats, which were reversed by treatment with
PDTC. Hypertensive rats developed pronounced cardiac
fibrosis with increased interstitial
collagen area, increased cardiac
reactive oxygen species levels,
gelatinase activity and MMP-2 expression.
PDTC treatment decreased these alterations. These findings show that
PDTC modulates myocardial MMP-2 expression and ameliorates cardiac remodelling in
renovascular hypertension. These results suggest that interfering with
MMP expression at transcriptional level may be an interesting strategy in the
therapy of organ damage associated with
hypertension.