Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries.
1. Pertussis toxin inactivates Gi-protein, which mediates the inhibitory effects of receptors on adenylate cyclase. The effects of the toxin on endothelium-dependent and independent relaxations were determined in porcine coronary arteries. 2. Arterial rings (with and without endothelium) were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution (maintained at 37 degrees C, gassed with 95% O2 and 5% CO2). 3. Incubation of the tissues with pertussis toxin (100 ng/ml for 60 min) virtually abolished the endothelium-dependent relaxations produced by the alpha 2-adrenergic agonist, UK 14304, and by 5-hydroxytryptamine. Endothelium-dependent relaxations to thrombin and to aggregating platelets were markedly reduced, whereas those produced by bradykinin were only minimally affected. Endothelium-dependent responses produced by the calcium ionophore (A23187) and by adenosine diphosphate were not altered by pertussis toxin. 4. Pertussis toxin did not affect the direct, endothelium-independent relaxations produced by nitric oxide, or by adenosine diphosphate. 5. These experiments demonstrate that pertussis toxin interferes with the release of endothelium-derived relaxing factor(s) evoked by certain, but not all, endothelial activators. The release of endothelium-derived relaxing factor(s) may occur through different pathways involving Gi-protein-dependent and independent mechanisms.
Flavahan
N A
NA
Department of Physiology and Biophysics, Mayo Clinic, Rochester, MN 55905.
Shimokawa
H
H
Vanhoutte
P M
PM
D037361:Adenylate Cyclase Toxin; D000818:Animals; D000068438:Brimonidine Tartrate; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010108:Oxyhemoglobins; D037342:Pertussis Toxin; D010974:Platelet Aggregation; D011810:Quinoxalines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013917:Thrombin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D010108:Oxyhemoglobins; D011810:Quinoxalines; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D000068438:Brimonidine Tartrate; D037342:Pertussis Toxin; D013917:Thrombin; D008751:Methylene Blue