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Hypertens Res. 2010 Oct;33(10):1071-81. doi: 10.1038/hr.2010.121. Epub 2010 Jul 29.

Is overall blockade superior to selective blockade of adrenergic receptor subtypes in suppressing left ventricular remodeling in spontaneously hypertensive rats?

Author information

1
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Shandong, PR China.

Abstract

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.

PMID:
20668454
DOI:
10.1038/hr.2010.121
[Indexed for MEDLINE]

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