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. 2013 Dec;34(12):1508-14.
doi: 10.1038/aps.2013.147. Epub 2013 Nov 18.

Ketanserin improves cardiac performance after myocardial infarction in spontaneously hypertensive rats partially through restoration of baroreflex function

Jian-guang Yu  1 , En-hui Zhang, Ai-jun Liu, Jian-guo Liu, Guo-jun Cai, Ding-feng Su
Affiliations

Ketanserin improves cardiac performance after myocardial infarction in spontaneously hypertensive rats partially through restoration of baroreflex function

Jian-guang Yu et al. Acta Pharmacol Sin. 2013 Dec.

Abstract

Aim: Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction (MI). Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved.

Methods: Spontaneously hypertensive rats (SHR) were treated with ketanserin (0.3 mg·kg(-1)·d(-1)). Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter (VAChT) and α7 nicotinic acetylcholine receptor (α7-nAChR) in ischemic myocardium, angiogenesis, cardiac function, and left ventricular (LV) remodeling were evaluated subsequently.

Results: Ketanserin significantly improved baroreflex sensitivity (0.62±0.21 vs 0.34±0.12 ms/mmHg, P<0.01) and vagal tonic activity (heart rate changes in response to atropine, 54.8±16.2 vs 37.6±13.4 bpm, P<0.01) without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin prominently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and α7-nAChR in ischemic myocardium.

Conclusion: Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI.

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Figures

Figure 1
Figure 1
Schematic diagram of the experimental protocol in this study.
Figure 2
Figure 2
Representative pictures of M-mode echocardiography in spontaneously hypertensive rats at 3 months after myocardial infarction with (C) or without (B) ketanserin treatment or sham operation (A).
Figure 3
Figure 3
Influence of ketanserin on angiogenesis in ischemic myocardium in spontaneously hypertensive rats with myocardial infarction. Ketanserin (0.3 mg·kg−1·d−1, delivered in food) increased capillary (arrows) density (A and B; at 2 weeks), regional blood flow (C; at 1 month), and VEGF expression (D; at 3 days) in ischemic myocardium. Scale bars=50 μm. n=8 in each group. bP<0.05, cP<0.01 vs MI. RBF, regional blood flow; IS, interventricular septum.
Figure 4
Figure 4
Effects of ketanserin on expression of vesicular acetylcholine transporter and α7 nicotinic acetylcholine receptor in ischemic myocardium in spontaneously hypertensive rats with myocardial infarction. Ketanserin (0.3 mg·kg−1·d−1, delivered in food) increased the expression of VAChT (A) and α7-nAChR (B) in ischemic myocardium at 1 week after myocardial infarction. Protein expression was shown as the relative change using MI rats as reference. n=6 in each group. cP<0.01 vs MI.
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