Endothelial cell calcium mobilization to acetylcholine is attenuated in copper-deficient rats.
Dietary copper deficiency significantly attenuates nitric oxide (NO)-mediated vascular smooth muscle relaxation and vasodilation. There is evidence for both increased inactivation of the NO radical by superoxide anion, and oxidative damage to the endothelium where NO is produced. The current study was designed to examine the NO synthetic pathway in the endothelium during copper deficiency. Male weanling rats were fed a copper-adequate (CuA, 6.4 mg Cu/kg diet) or copper-deficient (CuD, 0.4 mg Cu/kg diet) diet for four weeks. Cremasteric arterioles (approximately 100 microm diameter) were isolated and used for the experiments. Western blot analysis of the arteriole endothelial nitric oxide synthase (eNOS) concentration did not show a difference between dietary groups. Acetylcholine (Ach)-induced vasodilation was significantly reduced in the CuD group both before and after pretreatment with the eNOS substrate L-arginine. Endothelial intracellular calcium ([Ca2+]i) stimulated by 10(-6) M Ach was significantly inhibited in the arterioles from CuD rats. Coincident with the inhibition of [Ca2+]i and vasodilation was a depression of vascular Cu/Zn-SOD activity and an increase in plasma peroxynitrite activity. These data suggest that endothelial Ca2+ signaling and agonist-stimulated NO-mediated vascular dilation are likely reduced by increased oxidative damage in copper-deficient rats.
Schuschke
D A
DA
Center for Applied Microcirculatory Research, University of Louisville School of Medicine, KY 40292, USA. DASCHU01@GWISE.LOUISVILLE.EDU
Falcone
J C
JC
Saari
J T
JT
Fleming
J T
JT
Percival
S S
SS
Young
S A
SA
Pass
J M
JM
Miller
F N
FN
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001160:Arterioles; D002118:Calcium / Q000378:metabolism*; D003300:Copper / Q000172:deficiency*; D004032:Diet; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D009566:Nitrates; D016877:Oxidants; D014665:Vasodilator Agents; C039642:peroxynitric acid; D009569:Nitric Oxide; D003300:Copper; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D002118:Calcium