Nombre: JESSYCA APARECIDA SOARES GIESEN
Fecha de publicación: 12/12/2021
Junta de examinadores:
Nombre |
Papel |
|---|---|
| ALESSANDRA SIMAO PADILHA | Examinador Interno |
| ALICE VALENÇA ARAÚJO | Examinador Externo |
| NAZARE SOUZA BISSOLI | Examinador Interno |
| ROGER LYRIO DOS SANTOS | Presidente |
| SIMONE REGINA POTJE | Examinador Externo |
Sumario: Cardiovascular diseases (CVDs) have been the focus of numerous studies, and hypertension is considered one of the most prevalent risk factors for CVDs. The reduction in female sex hormones appears to be associated with an increased risk of developing CVDs, particularly due to the higher prevalence of hypertension. Among these hormones, progesterone seems to play a protective role that is not yet fully understood, especially in the coronary bed under hypertensive conditions. Thus, this study aimed to investigate the acute action of progesterone in the coronary vessels of spontaneously hypertensive rats (SHR) of both sexes and the potential mediators involved. Our hypothesis is that progesterone exerts a vasodilatory effect in the coronary bed and an anti-contractile effect in isolated coronary arteries of SHR of both sexes, and that this action involves different mediators. Spontaneously hypertensive rats (SHR) female and male, aged 12 weeks, were used (CEUA-UFES #24/2021). The estrous cycle of the females was monitored, and blood pressure was measured. After confirming hypertension, the action of progesterone was studied in the coronary bed using the Langendorff method and in isolated arteries through a wire myograph. NO levels were measured using DAF-2DA. In the coronary bed, the basal coronary perfusion pressure (CPP) was determined, and concentration-response curves to progesterone (0.1–50 M) were performed before and after perfusion with L-NAME, indomethacin (INDO), and clotrimazole (CLOT), individually or simultaneously, as well as with tiron, catalase, G36, and mifepristone (MIFE). In isolated arteries, contraction curves to 5-HT were constructed before and after incubation with DMSO, vehicle, and progesterone (10 and 50 M). Baseline CPP was lower in males than in females, and progesterone could promote similar vasodilation in both sexes. In females, progesterone-induced vasodilation was consistent across all phases of the estrous cycle. After L-NAME inhibition, an enhanced progesterone-induced relaxation effect was observed only in males. Following INDO inhibition, no differences were observed. However, simultaneous inhibition with L-NAME and INDO resulted in a decreased vasodilatory response in females and an enhanced relaxation in males. Reducing relation was relaxation was observed in females after inhibition with CLOT. When simultaneous inhibition with L-NAME, INDO, and CLOT was applied, females exhibited a further reduction in response, whereas males showed an enhanced response similar to L-NAME inhibition alone, but less pronounced than the combined L-NAME + INDO inhibition. After MIFE inhibition, only females exhibited a reduced response, while inhibition with G36 led to reduced responses in both males and females. The anti-contractile action of progesterone was observed in a concentration-dependent manner, with no sex differences. NO levels increased after progesterone stimulation similarly across groups. These findings suggest that progesterone modulates coronary vascular reactivity via vasodilatory actions mediated by distinct pathways, including prostanoids, EETs, and H2O2 in females, and NO and EETs in males. The nPRs appear to be involved in the observed relaxation exclusively in females, whereas GPER appears to play a role in both sexes. Progesterone-induced vasodilation in each sex may contribute to its anti-contractile effects. These findings contribute to a better understanding of progesterone's actions in the coronary bed and to the development of improved treatment strategies for both women and men with hypertension.
