Progesterone modulates endothelium-dependent coronary vascular reactivity in SHR

Abstract

Although progesterone has the ability to promote dilation of vascular smooth muscle, its role in coronary circulation is still poorly characterized, especially in essential hypertension and in a model of endogenous deficiency of ovarian hormones. Thus, this study evaluated the effect of progesterone treatment on endothelium-dependent coronary vascular reactivity in hypertensive (SHR) and ovariectomized rats. Adult SHR aged 8 to 10 weeks were divided into: SHAM, Ovariectomized (OVX) and Ovariectomized + treatment with 2 mg/kg/day of progesterone for 15 days (OVX-P4). Coronary vascular reactivity was investigated using modified Langendorff method. After stabilization, baseline coronary perfusion pressure (CPP) was recorded and vascular reactivity to bradykinin (BK, 0.1-1000 ng) assessed before and after infusion, either individually or in combination, with Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin or clotrimazole. Scanning electron microscopy was used for qualitative analysis of the endothelium. OVX and OVX-P4 groups had a higher baseline CPP compared to that of the SHAM group. BK was able to promote vasodilation in all groups. However, relaxation to BK was less pronounced in the OVX group when compared to SHAM, with architecture loss and areas of cell atrophy having been observed. Progesterone treatment prevented this injury. Perfusion with L-NAME induced greater damage to the SHAM group, while the use of indomethacin led to a significant reduction in the vasodilator response to BK in the OVX-P4 group. Taken together, our results show that progesterone modulates endothelium-dependent coronary vasodilation in SHR ovariectomized, preventing damage caused by ovarian hormonal deficiency through a mechanism that involves prostanoid pathway.

A mini-review of the evidence for cerebrovascular changes following gender-affirming hormone replacement therapy and a call for increased focus on cerebrovascular transgender health

“…For example, Gibson et al (2005) reports that administration of progesterone suppressed aspects of the post-injury inflammatory response, while Sunday et al (2006) found that the administration of progesterone exacerbated the inflammatory response in ovariectomized rats. However, there have been multiple reports of progesterone having a beneficial impact on recovery from brain injury (Chen et al, 2011(Chen et al, , 2021Gibson et al, 2011) and facilitating vascular reactivity (Cunha et al, 2020;da Costa et al, 2021).…”