Butyrate reduces blood pressure in hypertensive rats by activating the G protein-coupled receptor 41/43 pathway

doi:10.11958/20221713

Abstract

Abstract:

Objective To investigate the mechanism of butyrate reducing blood pressure in hypertensive model rats by activating G protein-coupled receptor 41/43 (GPR41/43) pathway. Methods Seventy-five male SD rats were randomly divided into the sham operation group (n=15) and the model group (n=60). Hypertensive rat model was established by two kidneys and one clip method. Model rats were randomly divided into the control group (0.1 mL/kg ultra-pure water), the butyrate high-dose group (220 mg/kg), the butyrate low-dose group (110 mg/kg) and the valsartan group (30 mg/kg), with 15 rats in each group. Rats were given intervention by cntinuous gavage for 4 weeks. Caudal artery systolic blood pressure (SBP) and heart rate (HR) were measured before and after administration. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and endothelial nitric oxide synthase (eNOS) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IL-6, TNF-α and eNOS in thoracic aorta were detected by real-time fluorescent quantitative PCR (qPCR). The expression of GPR41/43 in rat thoracic aorta was detected by immunohistochemistry. Results After 2 weeks of administration, SBP was significantly higher in the control group than that in the sham operation group (P<0.05). Values of SBP were significantly lower in the high dose butyrate group, the low dose butyrate group and the valsartan group than those in the control group, and SBP was significantly lower in the butyrate high dose group than that of the butyrate low dose group (P<0.05). After 4 weeks of administration, SBP was significantly lower in the high dose group than that in the low dose group (P<0.05). There were no significant differences in HR before and after administration between groups (P>0.05). After administration, the protein expression and mRNA expression of eNOS were increased in the butyrate high dose group and the butyrate low dose group compared with those of the control group, and the protein expression and mRNA expression of IL-6 and TNF-α were decreased (P<0.05). Immunohistochemistry showed that the expression of GPR41/43 in rat thoracic aorta tissue was increased compared with that of the control group, and which was higher than that in the valsartan group (P<0.05). Conclusion Butyrate has a significant antihypertensive effect on hypertensive rats, which may be related to the activation of GPR41/43 pathway to increase vasodilation and inhibit expression of inflammatory factors..

Key words: butyrates, hypertension, receptors, G-protein-coupled, interleukin-6, tumor necrosis factor-alpha, nitric oxide synthase type Ⅲ

CLC Number:

R349.6

Figures/Tables 6

References 19

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组别	造模前	造模4周	给药2周	给药4周
假手术组	100.3±7.2	100.2±4.8	99.9±5.9	101.5±6.4
对照组	99.7±6.8	154.9±8.2^a	152.7±5.9^a	153.4±5.4^a
缬沙坦组	100.6±7.8	156.8±9.2^a	143.0±10.2^ab	133.1±6.1^ab
丁酸低剂量组	101.6±5.6	159.5±10.6^a	144.5±9.2^ab	139.6±5.8^abc
丁酸高剂量组	100.4±5.5	159.4±8.9^a	138.7±6.3^abd	131.2±5.3^abd
F	0.181	129.073^＊＊	107.884^＊＊	160.446^＊＊

组别	造模前	造模4周	给药2周	给药4周
假手术组	100.3±7.2	100.2±4.8	99.9±5.9	101.5±6.4
对照组	99.7±6.8	154.9±8.2^a	152.7±5.9^a	153.4±5.4^a
缬沙坦组	100.6±7.8	156.8±9.2^a	143.0±10.2^ab	133.1±6.1^ab
丁酸低剂量组	101.6±5.6	159.5±10.6^a	144.5±9.2^ab	139.6±5.8^abc
丁酸高剂量组	100.4±5.5	159.4±8.9^a	138.7±6.3^abd	131.2±5.3^abd
F	0.181	129.073^＊＊	107.884^＊＊	160.446^＊＊

组别	造模前	造模4周	给药2周	给药4周
假手术组	337±41	347±65	348±72	349±35
对照组	344±63	372±46	373±36	381±27
缬沙坦组	336±48	373±39	368±53	358±61
丁酸低剂量组	349±37	373±37	367±57	364±43
丁酸高剂量组	341±45	374±42	362±60	358±47
F	0.214	0.873	0.457	1.167

组别	造模前	造模4周	给药2周	给药4周
假手术组	337±41	347±65	348±72	349±35
对照组	344±63	372±46	373±36	381±27
缬沙坦组	336±48	373±39	368±53	358±61
丁酸低剂量组	349±37	373±37	367±57	364±43
丁酸高剂量组	341±45	374±42	362±60	358±47
F	0.214	0.873	0.457	1.167

组别	eNOS	IL-6	TNF-α
假手术组	112.44±3.07	157.59±7.45	275.85±13.49
对照组	69.90±4.16^a	279.77±5.12^a	481.33±11.57^a
缬沙坦组	87.23±5.86^ab	238.73±10.25^ab	401.23±26.68^ab
丁酸低剂量组	79.87±5.60^abc	246.68±13.53^ab	456.36±24.84^abc
丁酸高剂量组	80.44±6.79^ab	230.55±14.13^abd	371.28±25.57^abcd
F	138.930^＊＊	256.736^＊＊	213.185^＊＊