title: Extracellular and intracellular alkalinization and the constriction of rat cerebral arterioles.
abstract: 1. Direct observations of perfused cerebral arterioles in vivo and in vitro have demonstrated that alkalinization of blood or cerebrospinal fluid (CSF) causes arteriolar constriction. Inasmuch as such alkalinizations lead to increases in intracellular pH (pHi) as well as interstitial pH (pHo), it is possible that increases in either pHi or pHo (or both) underlie alkalinization-induced cerebral vasoconstriction. In order to test the hypothesis that changes in pHi alone underline alkalinization-induced cerebral vasoconstriction, we simultaneously measured vessel diameter and pHi (using the pH-sensitive dye, SNAFL) in isolated cerebral arterioles from adult rats during imposed alterations in pHo and pHi. 2. Penetrating cerebral arterioles from the distribution of the middle cerebral artery were hand dissected, cannulated on one end and occluded distally. Vessels were inflated hydrostatically to 60 cmH2O under no-flow conditions. Confocal microscopy verified specific pH-sensitivity dye staining of the vascular smooth muscle cells within the vessel wall. 3. Extracellular alkalinization from pH 7.3 to 7.8 caused pHi to increase by 0.06 +/- 0.01 of a pH unit, and vessel diameter to decrease by 21.8 +/- 1.8% (mean +/- S.E.M.). 4. Intracellular alkalinization at constant pHo was produced by exposure to weak bases, including NH3 and trimethylamine, or by exposure to, followed by withdrawal of, weak acids, including CO2 and acetic acid. None of these treatments evoked vasoconstriction even though each of them caused increases in pHi greater than those observed in the same vessels during exposure to the pHo 7.8 solution. 5. We conclude that, at least in cerebral arterioles, alkalinization-induced vasoconstriction is mediated by an increase in pHo, not pHi [corrected].
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: M
authors.initials: M
authors.lastname: Apkon
authors.forename: W F
authors.initials: WF
authors.lastname: Boron
mesh_terms: D000468:Alkalies / Q000378:metabolism*; D000818:Animals; D001160:Arterioles; D002560:Cerebrovascular Circulation; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D051381:Rats; D014661:Vasoconstriction
chemical_list: D000468:Alkalies