19 October 2015
We investigate sensing and signaling mechanisms for H +, and CO 2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pH o, [ ] o, or pCO 2, we find: (a) lowering pH o attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca 2+-responses whereas raising pH o augments vasoconstriction independently of VSMC [Ca 2+] i, (b) lowering [ ] o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca 2+] i but c) no evidence that CO 2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects of are absent in arteries from RPTPγ-knockout mice. At pH o 7.4, selective changes in [ ] o or pCO 2 have little effect on pH i. At pH o 7.1, decreased [ ] o or increased pCO 2 causes intracellular acidification, which attenuates vasoconstriction. Under equilibrated conditions, anti-contractile effects of CO 2/ are endothelium-dependent and absent in arteries from RPTPγ-knockout mice. With CO 2/ present, contractile responses to agonist-stimulation are potentiated in arteries from RPTPγ-knockout compared to wild-type mice, and this difference is larger for respiratory than metabolic acidosis. In conclusion, decreased pH o and pH i inhibit vasoconstriction, whereas decreased [ ] o promotes vasoconstriction through RPTPγ-dependent changes in VSMC Ca 2+-sensitivity. serves dual roles, providing substrate for pH i-regulating membrane transporters and modulating arterial responses to acid–base disturbances.