U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade.
OBJECTIVE
We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein.


METHODS
Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension.


RESULTS
U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions.


CONCLUSIONS
U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.
Vila
J M
JM
Department of Physiology, University of Valencia School of Medicine, 46010, Valencia, Spain. vila@post.uv.es
Martínez-León
J B
JB
Medina
P
P
Segarra
G
G
Ballester
R M
RM
Otero
E
E
Lluch
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000368:Aged; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012501:Saphenous Vein; D013268:Stimulation, Chemical; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C054215:SQ 30741; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009543:Nifedipine; D009638:Norepinephrine