Acetate causes endothelium-independent increases in cyclic AMP in rat caudal artery.
The mechanism of the vasorelaxant action of acetate is unknown. Because cyclic nucleotides have been linked to vasorelaxation in vascular smooth muscle, we studied the effects of acetate on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels in rat caudal artery. Acetate (4 mM) induced an increase in tissue cAMP levels (control: 5.1 +/- 0.67, acetate: 7.1 +/- 0.97 pmol/mg protein, P less than 0.05), with the increase noted as early as 15-30 s after acetate exposure, and peaking at 60 s. The time course of the cAMP response was compatible with the vasorelaxant effect of acetate against an arginine vasopressin (AVP, 2 X 10(-9) M) contraction. Both the increase in cAMP and the vasorelaxant effect were completely blocked by 10(-3) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Acetate increased cAMP levels in 3-isobutyl-1-methylxanthine (IBMX)-treated tissue with an effective concentration producing 50% of the maximum response (EC50) of 1.5 mM, similar to the relaxant EC50 (without IBMX) of 2.2 mM against an AVP contraction. In other experiments, the effect of acetate on cAMP was shown to be independent of endothelium. In contrast, acetate had no effect on tissue cGMP levels, whether the endothelium was present or absent. The results suggest that acetate causes an increase in tissue cAMP levels that is not dependent on presence of a functioning endothelium. The changes in cAMP may be contributory to the vasorelaxant effect of acetate in the caudal artery.
Daugirdas
J T
JT
Department of Medicine, Hines Veterans Administration Hospital, Illinois 60141.
Swanson
V
V
Islam
S
S
Nutting
C
C
Kim
D D
DD
Wang
X A
XA
Fiscus
R R
RR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006157:Guanosine Monophosphate / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013623:Tail; D013806:Theophylline / Q000031:analogs & derivatives*
D000085:Acetates; D001127:Arginine Vasopressin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D006157:Guanosine Monophosphate; D013806:Theophylline; D000242:Cyclic AMP; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D015056:1-Methyl-3-isobutylxanthine