title: On the cellular mechanism for the effect of acidosis on vascular tone.
abstract: The role of smooth muscle [Ca2+]i and membrane potential for the relaxation to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarization plays an important role but this has not been vigorously tested. In this study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter was measured simultaneously with either [Ca2+]i or membrane potential, and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution or by adding HCI to a nominally bicarbonate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at transmural pressures between 20 and 120 mmHg. Acidification at a transmural pressure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+]i. This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+]i and depolarization, was also seen with reduction of pH in bicarbonate-free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapnic acidosis is most likely mediated by a reduction of [Ca2+]i. Membrane potential may on the other hand not play a major role for this reduction of [Ca2+]i and it is possible that molecular CO2 has an effect on the membrane potential.
authors.affiliation: Department of Pharmacology, University of Aarhus, Aarhus C, Denmark.
authors.forename: H L
authors.initials: HL
authors.lastname: Peng
authors.forename: A
authors.initials: A
authors.lastname: Ivarsen
authors.forename: H
authors.initials: H
authors.lastname: Nilsson
authors.forename: C
authors.initials: C
authors.lastname: Aalkjaer
mesh_terms: D000138:Acidosis / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002118:Calcium