Controle da ventilação em ratas wistar: efeito da progesterona endógena e exógena na quimiorrecepção ao CO2/pH

Abstract

Progesterone (P4) has a stimulating action on the respiratory system, and this action is verified, mediated by the progesterone receptor. In addition, estradiol (E2) is able to induce the formation of progesterone receptors, enhancing its effect. There are biological and pharmacokinetic differences between natural and synthetic (PS) P4 due to the different chemical formulas, despite these differences, PS is also capable of acting with a stimulating action on the respiratory system. Straus et al. in 2010 demonstrated partial recovery of chemosensitivity in two women with Congenital Central Hypoventilation Syndrome (CCHS) who used desogestrel a PS. Thus, natural and synthetic P4 have an action on the respiratory system. The study by Straus et al. was of great relevance because it demonstrated PS as a possible treatment measure for CCHS, a syndrome caused by a mutation in the PHOX2B gene, characterized by central hypoventilation due to reduced or absent ventilatory responses to hypercapnia. However, studies on the effects of P4 and PS on non-anesthetized in vivo animals are still scarce. Thus, our hypothesis is that hormone replacement with P4 or PS increases the ventilatory response to hypercapnia. Ventilatory measures were obtained by whole-body plethysmography in four conditions with progesterone oscillations: during the estrous cycle, pseudopregnancy, P4 replacement in ovariectomized animals, and with the use of PS ETOnogestrel (ETO), a metabolite of desogestrel. Our results showed that endogenous increase in P4 cannot alter the ventilatory response. However, in ovariectomized rats with P4 and E2 replacement (%V ̇ E 309.9±19.6) and in intact rats with ETO and E2 replacement (%V ̇ E 294.8±17.7) there was an increase in the ventilatory response to hypercapnia (p < 0.05), suggesting that both hormone replacements modulate an excitatory response of respiratory adjustments to hypercapnia.