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

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 (n¼16, 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 (Àdp/dt max ) rate of the LV pressure and LV relaxation time constant (s). The mRNA and protein expression levels of AR, protein kinase(PK) and G-protein subtypes, intracellular free calcium (Ca 2+ ) concentration and cardiocyte apoptoisis rate were determined. Three drug-treated groups showed higher velocity ratio of E wave to A wave (E/A) and Àdp/dt max and lower systolic blood pressure (SBP), LVMI, s, apoptosis rate and intracellular free Ca 2+ concentration than the no treatment group. The mRNA expression levels of AR-a 1B in the carvedilol group were significantly lower than the other two drug-treated groups. The mRNA expression levels of AR-b 1 , AR-b 2 and Gsa were significantly higher in the three drug-treated groups than in the no treatment group, with the expression levels of AR-b 2 being the highest in the carvedilol-treated group. The protein expression levels of PKA and PKC subtype a and d 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-a 1B and Gsa expression and increasing AR-b 2 expression.

Prenatal exposure to lipopolysaccharide results in myocardial remodelling in adult murine offspring

“…Previous studies demonstrated that apoptosis is involved in the cardiac remodelling and substantial loss of cardiomyocytes in genetic hypertension [36] and in renovascular hypertension [37]. Cardiomyocyte apoptosis enhances the cardiac remodelling of hypertensive rats and affects the cardiac interstitium [38]. Cardiomyocyte apoptosis induced by prenatal exposure to LPS may cause myocardial remodelling in the current study.…”

Chinese Classical Music Lowers Blood Pressure and Improves Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

“…The results of this study have important clinical significance in the treatment of hypertension complicated with respiratory diseases. It is known that the α1 receptor is mainly distributed in vascular smooth muscle, the β1 receptor is mainly distributed in cardiac muscle, and the β2 receptor is distributed in both vascular and bronchial smooth muscle ( O-Uchi and Lopes, 2010 ; Chen et al, 2010 ). As a result, patients with a combination of respiratory disease and hypertension have poor tolerance to non-selective beta blockers.…”

Combined blockade of β- and α1-adrenoceptors in left ventricular remodeling induced by hypertension: Beneficial or not?

“…In their study, Chen et al found decreases in the expression levels of b-ARs (b 1 -and b 2 -AR) due to enhanced sympathetic stimulation, which recovered spontaneously in hypertensive rats treated with AR antagonists. 10 Moreover, the expression level of b 2 -AR was increased in proportion to b 1 -AR in the carvedilol-treated group compared with animals treated with propranolol (a b 1 -and b 2 -AR antagonist); however, carvedilol is known to be relatively selective to b 1 -AR. 12 This specific recovery of b 2 -AR signaling by carvedilol may, in part, contribute to the attenuation of cardiomyocyte apoptosis.…”

“…9 Here, three important questions have been raised: (1) In this issue of Hypertension Research, Chen and colleagues test the hypothesis that non-selective AR blockade is more efficient in suppressing LV remodeling when compared with AR subtype-selective antagonists in a spontaneously hypertensive rat model. 10 A previous study compared non-AR subtype-selective and AR subtype-selective inhibition on LV dysfunction and remodeling induced by chronic coronary stenosis and coronary occlusion, 11 showing benefit from a non-selective inhibitor; however, a detailed mechanism was not investigated in that study. Chen and colleagues compared the effect of the b 1 -AR antagonist bisoprolol, the b 1 -and b 2 -AR antagonist propranolol and the a 1 -, b 1 -and b 2 -AR antagonist carvedilol on LV remodeling by hypertension (see also Figure 1).…”

“…2 In their study, Chen et al found that the expression level of a 1B -AR was significantly increased in spontaneously hypertensive rats, although a 1A -AR expression was not changed. 10 Moreover, the expression level of a 1B -AR and its downstream signaling pathways (PKCa and d) were normalized only in the carvediloltreated group. PKC represents a large gene family and has up to 12 isoforms, seven of which are expressed in the human heart.…”