Effects of progesterone treatment on endothelium-dependent coronary relaxation in ovariectomized rats

• Published in: Life sciences (1973) Vol. 247; pp. 117391 - 10
• Main Authors: Cunha, Tagana Rosa da, Giesen, Jéssyca Aparecida Soares, Rouver, Wender Nascimento, Costa, Eduardo Damasceno, Grando, Marcella Daruge, Lemos, Virgínia Soares, Bendhack, Lusiane Maria, Santos, Roger Lyrio dos
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.04.2020; Elsevier BV
• Subjects: AKT protein; Animals; Bradykinin; Cardiovascular system; Coronary reactivity; Coronary Vessels - drug effects; Endothelium; Endothelium, Vascular - drug effects; Female; Hydrogen peroxide; Hydrogen Peroxide - metabolism; NADPH Oxidase 2 - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Oophorectomy; Ovariectomized rats; Ovariectomy; Oxidative stress; Perfusion; Progesterone; Progesterone - pharmacology; Prostaglandins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Signal Transduction - drug effects; Superoxide anions; Superoxides - metabolism; Vasodilation; Vasodilation - drug effects; Western blotting; Progesterone; Coronary reactivity; Ovariectomized rats; Endothelium
• DOI: 10.1016/j.lfs.2020.117391
• ISSN: 0024-3205

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 (O2●-) and hydrogen peroxide (H2O2) 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.