Functional evidence that K+ is the non-nitric oxide, non-prostanoid endothelium-derived relaxing factor in rat femoral arteries.
The mechanisms of K(+)-induced relaxation and of acetylcholine (ACh)-stimulated, endothelium-dependent relaxation were assessed in rat femoral arteries mounted in a myograph. ACh-stimulated (1 nM-1 microM) relaxation of arteries precontracted with 1 microM noradrenaline was mostly resistant to the combination of indomethacin (INDO; 10 microM) and N(omega)-nitro-L-arginine (L-NNA, 100 microM). The remaining relaxation was abolished by 30 mM K(+) or ouabain (1 mM) and significantly reduced by 30 microM Ba(2+) or charybdotoxin (ChTx; 100 nM) plus apamin (100 nM). K(+)-induced relaxation effected by raising [K(+)](o) by 0.5-4 mM was endothelium-independent and inhibited by ouabain and Ba(2+). These results indicate that ACh-stimulated relaxations are effected mainly by a non-prostanoid, non-nitric oxide mechanism, presumably an endothelium-derived hyperpolarising factor (EDHF). Relaxations stimulated by EDHF and K(+) are both mediated by Na(+)-K(+) ATPase and inward rectifier potassium channels (K(IR)). This study provides further functional evidence that EDHF is K(+) derived from endothelial cells that relaxes arterial smooth muscle subsequent to activation of Na(+)-K(+) ATPase and K(IR).
Savage
Declan
D
Department of Human Anatomy and Physiology, University College Dublin, Ireland.
Perkins
Joanne
J
Hong Lim
Chin
C
Bund
Stuart J
SJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology* / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001685:Biological Factors; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000109:Acetylcholine; D011188:Potassium