Ex vivo study of the increased sensitivity to NO of endothelium-denuded thoracic aortas isolated from dietary magnesium-deficient rats.
The mechanisms underlying the enhanced relaxant responses to sodium nitroprusside (SNP) associated with magnesium (Mg) deficiency were examined using endothelium-denuded thoracic aortas isolated from rats with dietary Mg deficiency. This enhancement of SNP-induced relaxation was abolished or depressed in the presence of methylene blue (a guanylate cyclase inhibitor). The relaxant responses to 8-bromo cyclic GMP (8-Br cGMP; a membrane-permeable cGMP) of thoracic aortas isolated from Mg-deficient rats were enhanced like those to SNP. These enhanced relaxant responses were depressed by tetraethylammonium (a non-specific K+ channel blocker). Charybdotoxin, a large conductance Ca2+-activated K+ (K[Ca]) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient and control rats. Apamin, a small conductance K(Ca) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient, but not control rats. The relaxant responses to cromakalim (an ATP-sensitive K+ channel opener) of the two groups were not significantly different. These ex vivo results show that dietary Mg deficiency in rats leads to increased sensitivity to NO of endothelium-denuded thoracic aortas in vitro and K(Ca) channel activation via cGMP may be involved in this enhancement.
Ishiguro
S
S
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
Matsuyama
T
T
Sakaguchi
H
H
Nishio
A
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004032:Diet; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP; D008751:Methylene Blue