The Effect of Chemerin on Cardiac Parameters and Gene Expressions in Isolated Perfused Rat Heart

Abstract

Background: Chemerin is a novel chemoattractant adipokine expressed in cardiovascular system, and its receptor has been detected in the epicardial adipose tissue.

Aims: To determine the effects of chemerin on the cardiac parameters and gene expressions in the isolated perfused rat heart.

Study design: Animal experiment.

Methods: The hearts were retrogradely perfused with Langendorff technique to measure the cardiac parameters. The experimental groups were acutely treated with 10, 100, and 1000 nM doses of chemerin. Another group was given 10 μM L-nitric oxide synthase inhibitor for 5 min before 1000 nM chemerin administration. The real-time polymerase chain reaction was performed for detecting the expression of target genes.

Results: All doses of chemerin significantly decreased the left ventricular developed pressure (max 35.33 Δ%, p<0.001), and +dP/dt_max (max 31.3 Δ%, p<0.001), which are the indexes of cardiac contractile force. In addition, 1000 nM chemerin reduced the coronary flow (max 31 Δ%, p<0.001). N(W)-nitro-L-arginine methyl ester antagonized the negative inotropic effect of chemerin on contractility. Chemerin induced a 2.16-fold increase in endothelial nitric oxide synthase mRNA and increased the cyclic guanosine monophosphate levels (p<0.001) but decreased the PI3Kγ gene expression (1.8-fold, p<0.001). Furthermore, all doses of chemerin decreased the CaV1.2 gene expression (1.69-fold, p<0.001).

Conclusion: Acute chemerin treatment induces a negative inotropic action with the involvement of nitric oxide pathway, CaV1.2, and PI3Kγ on isolated rat heart.

Keywords: Animal experiment; chemerin; cyclic guanosine monophosphate; endothelial nitric oxide synthase; heart contractility.

Figure 1

Time-dependent effect of chemerin on the LVDP (a) and +dP/dtmax (b). Δ% refers to the change as a percentage of the 0 min value, that is, the value obtained prior to chemerin administration in chemerin-treated groups and the value obtained after a 30 min stabilization period in the control groups. -Δ% denotes the decrease. *p<0.05, **p<0.01, and ***p<0.001 significantly different from the respective controls. LVDP: left ventricular developed pressure

Figure 2

Time-dependent effect of chemerin on the heart rate (a) and coronary flow (b). Δ% indicates the change as a percentage of the 0 min value, that is, the value obtained prior to the administration of chemerin in the chemerin-treated groups and the value obtained after a 30 min stabilization period in the control groups. -Δ% shows the decrease. ***p<0.001 significantly different from the respective control.

Figure 3

Time-dependent effect of chemerin on the MAPamp (a) and MAP₉₀ (b). Δ% represents the change as a percentage of the 0 min value, that is, the value obtained prior to the administration of chemerin in chemerin groups and the value obtained after a 30 min stabilization period in the control groups. -Δ% and +Δ% show the decrease and increase, respectively. MAPamp: monophasic action potential amplitude; MAP₉₀ duration at 90% repolarization

Figure 4

Effects of the application of 10 μM dose of L-NAME and 10 μM dose of L-NAME with 1000 nM chemerin on the LVDP, +dP/dt_max, and coronary flow at 2 min (n=7). Δ% shows the decrease. a; p<0.001 significantly different than control group, b; p<0.001 significantly different than chemerin 1000 nM. A: Control, B: Chemerin 1000 nM, C: L-NAME 10 μM, D: L-NAME 10 μM + Chemerin1000 nM. LVDP: left ventricular developed pressure; L-NAME: N(W)-nitro-L-arginine methyl ester

Figure 5

Effects of chemerin on the cAMP (a) and cGMP (b) amounts in the left ventricular tissue. *p<0.05 significantly different from the control, n=7. cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate