| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2000;35:397.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Inhibition of cADP-Ribose Formation Produces Vasodilation in Bovine Coronary Arteries
From the Departments of Pharmacology and Toxicology and Physiology, Medical College of Wisconsin, Milwaukee, Wis.
Correspondence to Pin-Lan Li, MD, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail pli{at}mcw.edu
Abstract—cADP-ribose (cADPR) induces the release of Ca2+ from the intracellular stores of coronary artery smooth muscle cells. However, little is known about the role of cADPR-mediated intracellular Ca2+ 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 (IC50) 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 µmol/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 Ca2+ signaling pathway plays a role in the control of vascular tone in coronary circulation.
Key Words: adenosine diphosphate ribose • arteries • calcium channels • niacinamide
This article has been cited by other articles:
 |
|
 |
|
  T. L. Thai and W. J. Arendshorst ADP-ribosyl cyclase and ryanodine receptors mediate endothelin ETA and ETB receptor-induced renal vasoconstriction in vivo Am J Physiol Renal Physiol, August 1, 2008; 295(2): F360 - F368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Thai, S. K. Fellner, and W. J. Arendshorst ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1107 - F1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Fellner and W. J. Arendshorst Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in preglomerular arterioles Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1568 - F1572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zhang, G. Zhang, A. Y. Zhang, M. J. Koeberl, E. Wallander, and P.-L. Li Production of NAADP and its role in Ca2+ mobilization associated with lysosomes in coronary arterial myocytes Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H274 - H282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhang, E. G. Teggatz, A. Y. Zhang, M. J. Koeberl, F. Yi, L. Chen, and P.-L. Li Cyclic ADP ribose-mediated Ca2+ signaling in mediating endothelial nitric oxide production in bovine coronary arteries Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1172 - H1181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Fellner and L. Parker Endothelin-1, superoxide and adeninediphosphate ribose cyclase in shark vascular smooth muscle J. Exp. Biol., March 15, 2005; 208(6): 1045 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Laporte, A. Hui, and I. Laher Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle Pharmacol. Rev., December 1, 2004; 56(4): 439 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-X. Wang, Y.-M. Zheng, Q.-B. Mei, Q.-S. Wang, M. L. Collier, S. Fleischer, H.-B. Xin, and M. I. Kotlikoff FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells Am J Physiol Cell Physiol, March 1, 2004; 286(3): C538 - C546. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Kramm, B. Eberle, F. Krummenauer, S. Guth, H. Oelert, and E. Mayer Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy Ann. Thorac. Surg., September 1, 2003; 76(3): 711 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-X. Boittin, M. Dipp, N. P. Kinnear, A. Galione, and A. M. Evans Vasodilation by the Calcium-mobilizing Messenger Cyclic ADP-ribose J. Biol. Chem., March 7, 2003; 278(11): 9602 - 9608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-L. Li, W.-X. Tang, H. H. Valdivia, A.-P. Zou, and W. B. Campbell cADP-ribose activates reconstituted ryanodine receptors from coronary arterial smooth muscle Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H208 - H215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Jaggar and M. T. Nelson Differential regulation of Ca2+ sparks and Ca2+ waves by UTP in rat cerebral artery smooth muscle cells Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1528 - C1539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-L. Li, D. X. Zhang, Z.-D. Ge, and W. B. Campbell Role of ADP-ribose in 11,12-EET-induced activation of KCa channels in coronary arterial smooth muscle cells Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1229 - H1236. [Abstract] [Full Text] [PDF]
|
|