Al-Jarallah Aishah, Oriowo Mabayoje A
Departments of *Biochemistry; and †Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
J Cardiovasc Pharmacol. 2016 Feb;67(2):145-51. doi: 10.1097/FJC.0000000000000326.
The present investigation examined the effect of pregnancy on the anticontractile effect of perivascular adipose tissue (PVAT) on the rat. Ring segments of the aorta, with and without PVAT, were set up in organ baths for isometric tension recording. In both groups, concentration-response curves to 5-hydroxytryptamine (5-HT) were displaced to the right with a reduction of the maximum response in aorta segments with PVAT. The anticontractile effect of PVAT was attenuated on segments from pregnant rats. 4-Aminopyridine (4-AP), an inhibitor of voltage-gated potassium (Kv) channels, enhanced 5-HT-induced contractions of aorta segments from pregnant and nonpregnant rats only when PVAT was attached. There was no difference in the effect of 4-aminopyridine on 5-HT-induced contractions of aorta segments with PVAT from pregnant and nonpregnant rats. There was also no significant difference in the expression of Kv7.4 channels in aorta segments (with PVAT) between pregnant and nonpregnant rats. Tumor necrosis factor-α (TNF-α) was detected in PVAT from pregnant and nonpregnant rats. The level of TNF-α was significantly greater in PVAT from pregnant rats. Treatment of pregnant rats with pentoxyphyline significantly reduced the level of TNF-α in the PVAT and restored the anticontractile effect of PVAT on aorta segments from pregnant rats. Finally, TNF-α (10 ng/mL) potentiated 5-HT-induced contractions of PVAT-containing pregnant rat aorta. These results would suggest that the loss of anticontractile effect of PVAT in pregnant rat aorta could be due to enhanced production of TNF-α in the PVAT in these rats.
本研究考察了妊娠对大鼠血管周围脂肪组织（PVAT）抗收缩作用的影响。将带有和不带有PVAT的主动脉环段置于器官浴槽中进行等长张力记录。在两组中，5-羟色胺（5-HT）的浓度-反应曲线均向右移位，且带有PVAT的主动脉段的最大反应降低。PVAT对妊娠大鼠主动脉段的抗收缩作用减弱。4-氨基吡啶（4-AP）是电压门控钾（Kv）通道的抑制剂，仅在附有PVAT时增强妊娠和未妊娠大鼠主动脉段5-HT诱导的收缩。4-氨基吡啶对附有PVAT的妊娠和未妊娠大鼠主动脉段5-HT诱导收缩的作用没有差异。妊娠和未妊娠大鼠主动脉段（附有PVAT）中Kv7.4通道的表达也没有显著差异。在妊娠和未妊娠大鼠的PVAT中均检测到肿瘤坏死因子-α（TNF-α）。妊娠大鼠PVAT中TNF-α的水平显著更高。用己酮可可碱治疗妊娠大鼠可显著降低PVAT中TNF-α的水平，并恢复PVAT对妊娠大鼠主动脉段的抗收缩作用。最后，TNF-α（10 ng/mL）增强了附有PVAT的妊娠大鼠主动脉5-HT诱导的收缩。这些结果表明，妊娠大鼠主动脉中PVAT抗收缩作用的丧失可能是由于这些大鼠PVAT中TNF-α产生增加所致。
