Gomes-Pereira Leonardo, da Silva-Santos José Eduardo
Department of Pharmacology, Laboratory of Cardiovascular and Smooth Muscle Biology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Br J Pharmacol. 2025 Oct;182(19):4535-4552. doi: 10.1111/bph.70095. Epub 2025 Jun 9.
Although perivascular adipose tissue (PVAT) contains substances with contractile properties, its actions on the vascular tone are associated with the release of anticontractile substances. We hypothesize that procontractile PVAT products also exert direct effects on vascular tone.
Thoracic aortas from Wistar rats, with (E+) and without (E-) functional endothelium, were mounted in organ baths. Thoracic PVAT sections were incubated in physiological salt solution (PSS, 37°C or 70°C), yielding the PSSt(+)PVAT, which was transferred (t) to the organ baths and analysed for noradrenaline content.
Transfer (t) of the PSSt(+)PVAT solution induced a sustained vasoconstriction, three times greater in E- than in E+ aortic rings. The contractile action of the thoracic PVAT did not differ between male and female rats and was also induced by abdominal and mesenteric PVAT. Exposure to heat (70°C) increased PVAT-induced vasoconstriction by ~25 and 300% in E- and E+ rings, respectively. Incubation of PVAT with guanethidine increased the procontractile effects of PSSt(+)PVAT. Guanethidine also promoted vasoconstriction in aortic rings fully attached to PVAT. The contractile responses evoked by PVAT were abolished by prazosin, an α-adrenoceptor antagonist. Immunoassay detection revealed that the contractile effects mediated by the PSSt(+)PVAT correlate with spontaneous or experimentally induced noradrenaline release by PVAT.
Using functional and transfer bioassay approaches, we showed that the PVAT from healthy rats can exert direct contractile effects in the thoracic aorta. Pharmacological approaches and quantitative determination indicate that the release of noradrenaline accounts for this action.
尽管血管周围脂肪组织(PVAT)含有具有收缩特性的物质,但其对血管张力的作用与抗收缩物质的释放有关。我们推测,促收缩性PVAT产物也对血管张力有直接影响。
将具有(E+)和不具有(E-)功能性内皮的Wistar大鼠胸主动脉安装在器官浴槽中。将胸段PVAT切片在生理盐溶液(PSS,37°C或70°C)中孵育,得到PSSt(+)PVAT,将其转移(t)至器官浴槽并分析去甲肾上腺素含量。
PSSt(+)PVAT溶液的转移(t)引起持续的血管收缩,在E-主动脉环中比在E+主动脉环中大三倍。胸段PVAT的收缩作用在雄性和雌性大鼠之间没有差异,并且也由腹段和肠系膜PVAT诱导。暴露于热(70°C)分别使E-和E+环中PVAT诱导的血管收缩增加约25%和300%。用胍乙啶孵育PVAT增加了PSSt(+)PVAT的促收缩作用。胍乙啶还促进了完全附着于PVAT的主动脉环中的血管收缩。PVAT引起的收缩反应被α-肾上腺素能受体拮抗剂哌唑嗪消除。免疫测定检测显示,PSSt(+)PVAT介导的收缩作用与PVAT自发或实验诱导的去甲肾上腺素释放相关。
使用功能和转移生物测定方法,我们表明健康大鼠的PVAT可在胸主动脉中发挥直接收缩作用。药理学方法和定量测定表明,去甲肾上腺素的释放是这种作用的原因。