Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries.
The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and pHo was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation to normocapnic acidosis. Predominant extracellular acidosis, induced by reducing [HCO3-] from 25 to 9 mmol/L and CO2 from 5% to 2.5%, also caused inhibition of tension in steady state. By contrast, predominant intracellular acidosis, induced by increasing [HCO3-] from 25 to 65 mmol/L and CO2 from 5% to 15%, induced a small increase of basal tension and a small decrease of tension in the presence of arginine vasopressin. The responses to predominant intracellular or extracellular acidosis were qualitatively similar in the presence and absence of endothelium and in the presence and absence of N-nitro-L-arginine. It is concluded that the extracellular acidosis and not smooth muscle intracellular acidosis is responsible for the relaxation to hypercapnic acidosis.
Department of Pharmacology, University of Aarhus, Denmark.
R
R
Tian
P
P
Vogel
N A
NA
Lassen
M J
MJ
Mulvany
F
F
Andreasen
C
C
Aalkjaer
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002536:Cerebral Arteries / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014664:Vasodilation