Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Life Sci. 2020 Apr 15;247:117391. doi: 10.1016/j.lfs.2020.117391. Epub 2020 Feb 1.
Although progesterone (P4) has a beneficial effect on the cardiovascular system, P4 actions on the coronary bed have not yet been fully elucidated. This study evaluated the effect of progesterone treatment on endothelium-dependent coronary vascular reactivity in Wistar rats.
Eight-week-old adult rats were divided into Sham, Ovariectomized (OVX), Ovariectomized and progesterone treated (OVX P4). The OVX P4 group received daily doses of progesterone (2 mg/kg/day). Vascular reactivity was assessed by a modified Langendorff technique. The intensity of eNOS, Akt, and gp91phox protein expression was quantified by Western blotting. Superoxide anion (O) and hydrogen peroxide (HO) production was measured by dihydroethidium and 2',7'-dichlorofluorescein, respectively.
Treatment with P4 was able to prevent the reduction in baseline coronary perfusion pressure induced by ovariectomy. We observed that endothelium-dependent coronary vasodilation was reduced in the OVX group and potentiated in the OVX P4 group. Following the inhibition of the nitric oxide (NO) pathway, the bradykinin-induced relaxing response was potentiated in the OVX P4 group. With regard to the combined inhibition of NO and prostanoids pathways, the OVX P4 group showed a greater relaxing response, similar to what was found upon individual inhibition of NO. After the combined inhibition of NO, prostanoids and epoxyeicosatrienoic acids' pathways, the vasodilatory response induced by BK was abolished in all groups.
Treatment with P4 prevented oxidative stress induced by ovariectomy. These results suggest that progesterone has a beneficial action on the coronary vascular bed.
尽管孕酮（P4）对心血管系统有有益的作用，但 P4 对冠脉床的作用尚未完全阐明。本研究评估了孕酮治疗对 Wistar 大鼠内皮依赖性冠脉血管反应性的影响。
将 8 周龄成年大鼠分为假手术组、卵巢切除组（OVX）、卵巢切除和孕酮治疗组（OVX P4）。OVX P4 组每天给予孕酮（2 mg/kg/天）。通过改良的 Langendorff 技术评估血管反应性。通过 Western blot 定量测定 eNOS、Akt 和 gp91phox 蛋白的表达强度。通过二氢乙啶和 2',7'-二氯荧光素分别测量超氧阴离子（O）和过氧化氢（HO）的产生。
孕酮治疗能够预防卵巢切除引起的基础冠脉灌注压降低。我们观察到，内皮依赖性冠脉血管舒张在 OVX 组中减少，而在 OVX P4 组中增强。在抑制一氧化氮（NO）途径后，在 OVX P4 组中，缓激肽诱导的舒张反应增强。对于同时抑制 NO 和前列腺素途径，OVX P4 组显示出更大的舒张反应，类似于单独抑制 NO 时的反应。在同时抑制 NO、前列腺素和环氧二十碳三烯酸途径后，所有组的 BK 诱导的血管舒张反应均被消除。
孕酮治疗预防了卵巢切除引起的氧化应激。这些结果表明，孕酮对冠脉血管床具有有益的作用。
