To test the hypothesis that nonselective blockade of
adrenergic receptor (AR) subtypes is superior to selective blockade of AR subtypes in suppressing left ventricular (LV) remodeling induced by
hypertension. Sixty-four spontaneously hypertensive rats (SHR) were randomly divided into four groups:
bisoprolol-treated,
propranolol-treated,
carvedilol-treated and no treatment groups (n=16, each). Sixteen Wistar-Kyoto (WKY) rats served as a control group. Echocardiography and cardiac catheterization were carried out to record the mitral flow velocity ratio of E wave to A wave (E/A), LV mass index (LVMI), maximal rising (dp/dt(max)) and falling (-dp/dt(max)) rate of the LV pressure and LV relaxation time constant (τ). The
mRNA and
protein expression levels of AR,
protein kinase(PK) and
G-protein subtypes, intracellular free
calcium (Ca) concentration and cardiocyte apoptoisis rate were determined. Three
drug-treated groups showed higher velocity ratio of E wave to A wave (E/A) and -dp/dt(max) and lower systolic blood pressure (SBP), LVMI, τ, apoptosis rate and intracellular free Ca(2+) concentration than the no treatment group. The
mRNA expression levels of AR-α(1B) in the
carvedilol group were significantly lower than the other two
drug-treated groups. The
mRNA expression levels of AR-β(1), AR-β(2) and Gsα were significantly higher in the three
drug-treated groups than in the no treatment group, with the expression levels of AR-β(2) being the highest in the
carvedilol-treated group. The
protein expression levels of PKA and PKC subtype α and δ were lower in the three
drug-treated groups than in the no treatment group. Overall blockade of AR subtypes is not superior to selective blockade of AR subtypes in suppressing LV remodeling in SHR. Although
carvedilol is the most effective in attenuating cardiocyte apoptosis, normalizing AR-α(1B) and Gsα expression and increasing AR-β(2) expression.