Effect of palytoxin on endothelium-dependent and -independent relaxation in rat aortic rings.
Endothelium-intact rat aortic rings were incubated with palytoxin (PTX, 10(-11)-10(-9)M, 10 min) in oxygenated (O2 95%, CO2 5%) baths. Phenylephrine (PE)-contracted vascular rings demonstrated decreasing relaxation to acetylcholine (ACh), depending upon PTX incubation in a dose-dependent manner; however, sodium nitroprusside (NaNP) persisted in returning the ring to its pre-PE tension. After incubation with PTX, relaxation to the receptor-independent, endothelium-dependent relaxant A23187 was also attenuated. Thus, endothelium-dependent mechanism(s) normally responsive to both ACh and A23187, stimulators of nitric oxide (NO) release, were disrupted. Following incubation with PTX, endothelium-independent relaxation to NaNP remained intact but relaxation to atriopeptin II (APII) decreased. Electron microscopy demonstrated microvesiculation of endothelial cell cytoplasm and an irregular luminal surface following incubation with PTX. The intact response to NaNP, despite the loss of relaxation to ACh, indicated that soluble guanylate cyclase was not affected by PTX. However, loss of relaxation to AP-II, involving particulate guanylate cyclase of vascular smooth muscle (VSM), was inhibited by PTX pre-incubation. Determination of the site(s) of action of PTX requires further study.
Taylor
T J
TJ
Toxinology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
Smith
N C
NC
Langford
M J
MJ
Parker
G W
GW
D000109:Acetylcholine / Q000494:pharmacology; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000633:toxicity*; D003600:Cytosol / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D000095702:Polyether Toxins
D000109:Acetylcholine; D000178:Acrylamides; D009320:Atrial Natriuretic Factor; D000001:Calcimycin; D003064:Cnidarian Venoms; D006162:Guanylate Cyclase; D009569:Nitric Oxide; D009599:Nitroprusside; D010446:Peptide Fragments; D010656:Phenylephrine; C062524:atrial natriuretic factor prohormone (103-125); C010272:palytoxin; D000095702:Polyether Toxins