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Inhibition of cADP-ribose formation produces vasodilation in bovine coronary arteries. Hypertension 2000 Jan;35(1 Pt 2):397-402



Pubmed ID




Scopus ID

2-s2.0-0033978260   49 Citations


cADP-ribose (cADPR) induces the release of Ca(2+) from the intracellular stores of coronary artery smooth muscle cells. However, little is known about the role of cADPR-mediated intracellular Ca(2+) release in the control of vascular tone. The present study examined the effects of nicotinamide, a specific inhibitor of ADP-ribosylcyclase, on the vascular tone of bovine coronary arteries. A bovine coronary artery homogenate stimulated the conversion of nicotinamide guanine dinucleotide into cGDP-ribose, which is a measure of ADP-ribosylcyclase activity. Nicotinamide significantly inhibited the formation of cGDP-ribose in a concentration-dependent manner: at a concentration of 10 mmol/L, it reduced the conversion rate from 3.34+/-0.11 nmol. min(-1). mg(-1) of protein in control cells to 1.42+/-0.11 nmol. min(-1). mg(-1) of protein in treated cells, a 58% reduction. In U46619-precontracted coronary artery rings, nicotinamide produced concentration-dependent relaxation. Complete relaxation with nicotinamide occurred at a dose of 8 mmol/L; the median inhibitory concentration (IC(50)) was 1.7 mmol/L. In the presence of a cell membrane-permeant cADPR antagonist, 8-bromo-cADPR, nicotinamide-induced vasorelaxation was markedly attenuated. Pretreatment of the arterial rings with ryanodine (50 micromol/L) significantly blunted the vasorelaxation response to nicotinamide. However, iloprost- and adenosine-induced vasorelaxation was not altered by 8-bromo-cADPR. Moreover, nicotinamide significantly attenuated KCl- or Bay K8644-induced vasoconstriction by 60% and 70%, respectively. These results suggest that the inhibition of cADPR formation by nicotinamide produces vasorelaxation and blunts KCl- and Bay K8644-induced vasoconstriction in coronary arteries and that the cADPR-mediated Ca(2+) signaling pathway plays a role in the control of vascular tone in coronary circulation.

Author List

Geiger J, Zou AP, Campbell WB, Li PL


William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
ADP-ribosyl Cyclase
Adenosine Diphosphate Ribose
Calcium Channel Agonists
Calcium Channels
Coronary Circulation
Coronary Vessels
Cyclic ADP-Ribose
Phosphorus-Oxygen Lyases
Potassium Chloride
Vasodilator Agents
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b