Fig. 5.

Scheme for the potential effects of betamethasone exposure on the ANG II and Ang-(1–7) pathways to influence Na⁺ transport in the tubule cells. A: ANG II binds to the AT₁ receptor (AT₁R) and may stimulate protein kinase C (PKC) and NADPH oxidase (NOX) to generate reactive oxygen species (ROS) that activates the mitogen-activated pathway (MAPK) to stimulate Na⁺ uptake in the tubules (40). In contrast, Ang-(1–7) binds to the AT₇-Mas-R to stimulate nitric oxide synthase (NOS) to generate NO and increase cellular levels of cGMP by soluble guanylate cyclase (sGC) to stimulate protein kinase G to inhibit Na⁺ uptake. Angiotensin-converting enzyme 2 (ACE2), expressed on the apical face of the tubules, metabolizes ANG II to Ang-(1–7) and may influence both ANG II and Ang-(1–7) tone. In the Beta-exposed males, expression of the AT₁R is higher (52) and may promote greater Na⁺ uptake. In contrast, both ACE2 (51) and the AT₇-Mas-R expression are lower in the tubules that would attenuate the Ang-(1–7) tone and reduce Na⁺ uptake. Betamethasone exposure may also attenuate NO generation and PKG responsiveness that may further influence Na⁺ handling in the male tubules.