Differential effects of deleting the angiotensin receptor AT on the whole animal response to respiratory and metabolic acidosis in mice.

During systemic acid-base disturbances, the respiratory system modulates CO elimination, whereas the urinary system modulates H secretion-responses that tend to stabilize arterial pH (pH). Proximal tubules (PTs) are responsible for ∼80% of renal H secretion. Isolated PTs appear to sense and respond to acute changes in basolateral [CO] or [[Formula: see text]] using a mechanism that signals through apical angiotensin II AT receptors. In the present study, we examine the whole animal responses to both respiratory acidosis (RAc: ↑[CO] → ↓pH) and metabolic acidosis (MAc: ↓[[Formula: see text]] → ↓pH) in wild-type (WT) versus AT knockout (KO) mice. After catheterizing the carotid artery, we serially sample blood for arterial blood-gas analyses. We find that, in mice breathing 8% CO, pH reaches a nadir at ∼5 min, and begins to recover after ∼4 h, reaching its maximal value by ∼24 h. Surprisingly, we find that the KO of AT does not affect RAc compensation. During MAc (1% NHCl in drinking water), WT males exhibit only a small/insignificant fall in pH, whereas WT females exhibit a larger/significant pH decrease. In another sexual dimorphism, AT-KO males acidify on of MAc, but nearly recover by , whereas KO females exhibit either of two responses: ) adaptive, in which pH falls relatively little by and then recovers by , and ) maladaptive, in which pH falls at and remains depressed at . Thus, AT is crucial for defense against MAc in all but half the females, but not RAc. Here, for the first time, we report that the compensatory response to respiratory acidosis (RAc) in conscious mice concludes within 24 h. Interestingly, during the assessment of metabolic acidosis (MAc), we show that WT males are more adaptive than females, and observe two subpopulations of AT-KO females. From measurements of arterial pH, we conclude that AT is not necessary for the compensation to RAc, but is necessary in the response to MAc.