The vasorelaxant effects of acetate: role of adenosine, glycolysis, lyotropism, and pHi and Cai2+.
The mechanism of acetate vasorelaxation is unknown. In the rat caudal artery, acetate has a vasorelaxant effect and also increases cyclic AMP. Here we evaluate the role of adenosine, of possible glycolysis inhibition by acetate, of the lyotropic properties of acetate and other anions, and of intracellular calcium and pH. Adenosine per se did not relax the caudal artery in the range of 10(-8) to 10(-2) M. Preincubation with adenosine deaminase (ADA, 5.0 U/ml) or with 8-phenyltheophylline (8-PT, 10(-6) to 10(-4) M) increased, rather than blocked the vasorelaxant effect of acetate. Oxypurinol (10(-3) M) or the nucleoside transport inhibitor NBMPR (10(-4) M) had no effect on acetate relaxation. Whereas acetate increased tissue cyclic AMP content, 10(-3) M adenosine or 10(-6) M PIA had no effect. In strips studied under conditions of inhibited glycolysis (no glucose, with 11 mM 2-deoxyglucose, 1.0 mM pyruvate, and 0.5 mM 5-iodoacetate), acetate-induced relaxation, as well as acetate-induced cyclic AMP generation, tended to be reduced but not significantly so. Other anions relaxed vascular strips in relation to their lyotropic number, but only at higher doses, and they did not stimulate cyclic AMP formation. Acetate (10 mM) caused a transient fall in Ca2+i followed by a slight, sustained rise. A concomitant decrease in pHi was seen. DIDS, which blocks the relaxant and cyclic AMP effects of acetate, had no effect on the pHi decrease, but did decrease the rate of pHi recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Nutting
C W
CW
Department of Research and Medicine, Westside VA Medical Center, Chicago, Illinois.
Islam
S
S
Ye
M H
MH
Batlle
D C
DC
Daugirdas
J T
JT
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012995:Solubility; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000085:Acetates; D000242:Cyclic AMP; D000241:Adenosine; D019342:Acetic Acid; D002118:Calcium