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[Alterations in aortic vasomotor function in rats with chronic heart failure and its mechanism.] [Ariticle in Chinese]

ZHANG Hong-Li, ZHAO Ming, HE Xi, JIANG Hong-Ke, YU Xiao-Jiang, MA Xin, ZANG Wei-Jin^*

Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China

Abstract

The aim of the present study was to investigate the alterations in thoracic aortic vasomotor function in rats with chronic heartfailure (CHF) post myocardial infarction (MI), and then explored the possible mechanism of pathological changes. Male Sprague-Dawley rats were divided into sham and CHF groups randomly. The CHF model group of rats was generated by ligating the left anteriordescending artery. In sham-operated rats the ligation was placed but not tightened. A total of 20 rats underwent either sham-operated(n=8) or surgery for MI (n=12). All sham-operated rats survived the surgical procedure and the post-surgical period, whereas totalmortality among MI-rats was 25% (3 out of 12). Only MI-rats with infarct-size >30% of the left ventricle (LV) were included foranalysis (8 out of 9). Ten weeks after surgery, rats were anaesthetized for hemodynamic measurements, which contains systolicpressure, diastolic pressure, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV+dp/dtmax andLV-dp/dtmax. After that hearts were rapidly excised and weighed. Myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining method. Isolated thoracic artery ring preparations were studied in a wire-myograph. The arterial constrictiveresponses to KCl, CaCl2, phenylephrine (PE), and caffeine and the arterial diastolic responses to acetylcholine (ACh) were recorded bythe Multi Myograph System. To explore the possible mechanism, nitric oxide synthase (NOS) inhibitor N-nitrl-L-arginine methylester(L-NAME) and non-selective cyclooxygenase (COX) inhibitor indomethacin (Indo) were used. The results obtained were as follows:(1) CHF group showed an increased contraction response to KCl (5 – 100 mmol/L) and PE (1×10-8–3×10-4 mol/L), and a reducedendothelium-dependent relaxation response to ACh (1×10-12–1×10-4 mol/L) compared with those observed in sham group (P<0.01, P<0.05);(2) In the presence of L-NAME (1 mmol/L), the endothelium-dependent cumulative contractions to ACh (1×10-7–1×10-4 mol/L) wassignificantly enhanced in CHF group (P<0.05), and this effect was reversed by pretreatment with Indo (10 μmol/L); (3) In CHF group,the vessels incubated with Indo (10 μmol/L) showed an increased vasodilation induced by ACh (1×10-12–1×10-4 mol/L) (P<0.05); (4) Inthe Ca2+-free K-H solution, calcium-dependent contraction curves induced by CaCl2 (1×10-4–3×10-2 mol/L) in CHF group significantlyshifted to the left compared with sham group (P<0.05); while the vascular contraction induced by caffeine (30 mmol/L) had nosignificant changes. These findings suggest that thoracic arteries of rats with CHF have endothelial dysfunction, and the contributionof endothelial dilation and contraction was significantly altered in CHF rats. The mechanism could be partly associated with theincreased endothelium-dependent contracting factors by COX pathway, or the increased extracellular Ca2+ influx through voltageoperatedchannels, thus leading to elevated vasoconstriction.

Key words: chronic heart failure; thoracic artery; endothelial dysfunction; cyclooxygenase; calcium

Received: 2010-03-17　　Accepted: 2010-05-27

Corresponding author: 臧伟进　　E-mail: zwj@mail.xjtu.edu.cn

Citing This Article：

ZHANG Hong-Li, ZHAO Ming, HE Xi, JIANG Hong-Ke, YU Xiao-Jiang, MA Xin, ZANG Wei-Jin. [Alterations in aortic vasomotor function in rats with chronic heart failure and its mechanism.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (4): 317-324 (in Chinese with English abstract).