Estradiol e canal TRPV1 contribuem para o controle vasomotor e fluxo sanguíneo da artéria da cauda: consequências para a dissipação de calor em ratas

Abstract

The autonomic regulation of vasomotor tonus defining the blood flow to periphery is part of neural mechanism triggered to maintain body temperature within narrow values. However, in some physiological and/or pathological conditions body temperature may raise, causing disturbances that may be uncomfortable, such as hot flashes and fever. The estradiol (E2) and Transient Receptor Potential Vanilloid-type 1 (TRPV1) channel are known to participate in the thermoregulation. Therefore, the present study test whether E2 and TRPV1 are essential for the cutaneous tonus vasomotor in a way that increase blood flow to tail artery favoring heat dissipation in female rats. For that, adult Wistar rats were ovariectomized (OVX) and treated with E2 or oil. Desensitization and activation of the TRPV1 channel were the pharmacological strategies used to evaluate the contribution of this channel (CEUA: 99/2018). The identification of estrogen receptors (ER) in the tail artery points to a possible direct action of estradiol (E2) in this vascular bed, which is the main route of heat dissipation of rats. In addition, OVX+E2 rats showed increased basal blood flow in this vessel. On the other hand, the desensitization of the TRPV1 channel reduced this flow, even in the presence of E2, showing the importance of this channel in this process. To evaluate whether E2 alters the sympathetic efference that reaches the nerve endings of the tail artery, the expression of tyrosine hydroxylase (TH), a limiting enzyme of catecholamine biosynthesis, was evaluated. Treatment with E2 reduced the expression of this protein in the tail artery, suggesting a possible mechanism by which E2 contributes to a greater basal asodilation. Another E2 target investigated was nitric oxide (NO), whose vasodilator action is already described in other vascular beds. Interestingly, E2 also increased the amount of this molecule in the tail artery, which also may explain the increased vasodilation in the OVX+E2 group. The presence of ER-α, TRPV1 and TH was identified in the dorsal root ganglion (DRG), a component of the afferent pathway of thermoregulation. In this region, E2 was capable of reducing the expression TRPV1. On the other hand, the hypothermia induced by TRPV1 activation was more quickly reverted in ovary-intact rats, which suggest a participation of ovarian steroids on this response. However, TRPV1 activation did not alter the expression of TH either in OVX or ovary-intact rats, suggesting that the TRPV1-recruited pathways regulating heat dissipation may differ from those of E2. Finally, we evaluated the thermoregulatory responses of OVX ratsthat had the TRPV1 channel desensitized to a warming environment (34°C, 40 min). Compared to vehicle, TRPV1 desensitized rats showed a large increase in the core body temperature that was not accompanied by an increase in tail temperature. In addition, TRPV1-desensitized OVX rats showed high threshold and reduced sensitivity in heat dissipation. Together these results show that E2 and TRPV1 are important for maintaining cutaneous vasomotor tone and blood flow of the tail artery, in a such way that favors heat dissipation. E2 and TRPV1 thermoregulation may be through different molecular targets.