The physicochemistry of [H+] and respiratory control: roles of PCO2, strong ions, and their hormonal regulators.

I describe how the dietary intake of strong ions potentially affects the regulation of ventilation and the PCO2 of body fluids in two ways. First, changing the dietary intake of NaCl can alter the concentration difference between strong cations and strong anions (the [SID] of Stewart) of body fluids. Experimental observations indicate that the [SID] in brain fluids or cerebrospinal fluid ([SID]CSF) could be the stimulus to central chemoreceptors. [SID]CSF consistently predicts ventilatory regulation of PCO2, whereas [H+]CSF does not. PCO2 acts as a stimulus to ventilation independently of [SID]CSF and possibly at higher as well as lower centers of the nervous system. I relate the concept of [SID] regulation of arterial PCO2 to the alphastat hypothesis of protein function, respiratory control, and [H+] homeostasis. Second, altering the dietary intake of NaCl changes the levels of hormones involved in salt and water balance. Angiotensin II acts centrally to stimulate ventilation. Evidence for the roles of both the renal and brain renin-angiotensin systems in respiratory control, and the modulation of respiratory control by vasopressin are reviewed. These peptide systems probably act via circumventricular organs of the brain to affect respiratory control and (or) by changing strong ion concentrations in brain fluids. Questions to be resolved on the role of [SID]CSF and hormones in respiratory adaptations, and experiments required to improve our understanding of the control of ventilation, are addressed in the concluding comments.