Thromboxane A2 in vasomotor effects of phenylephrine, acetylcholine, and bradykinin in rat mesenteric bed.
In vessels, pharmacological agents displace the balance between relaxing and contracting factors. A cross-talk between those factors has been shown in some vascular beds. To examine whether NO may regulate the vascular tone by modulating prostanoid synthesis or release, we analyzed the response of resistance rat mesenteric arterial bed to vasoactive agents. Phenylephrine, bradykinin (BK), and acetylcholine (ACH) were administered in the absence or in the presence of either NO synthesis inhibition (N(G)-nitro-L-arginine methyl ester [L-NAME]), cyclo-oxygenase inhibition (indomethacin), and/or a thromboxane A2 (TXA2) receptor antagonist (S18886), or a combination thereof. In the presence of L-NAME, the response to phenylephrine was markedly increased. Indomethacin limited these changes, which are attributed to TXA2 release since they were abolished by S18886 and a marked increase in TXB2 release (stable metabolite of TXA2) was found during phenylephrine infusion under NO blockade. Similarly, BK response under NO blockade was markedly attenuated with an improved response with indomethacin and a restoration of vasorelaxation with S18886. In contrast, indomethacin decreased further the response to ACH during L-NAME treatment, and TXA2 inhibition had no effect. Thus, in pathophysiological conditions where an endothelial dysfunction is present, TXA2 stimulation induced by NO release impairment may contribute to an altered response to phenylephrine or BK.
Unité INSERM U 400, Faculté de Médecine, 8 rue du Général, Sarrail 94000, France.
Rachid
R
Ben Cheikh
Jean-Claude
JC
Féray
Abdelillah
A
Alaoui
Bertrand
B
Crozatier
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013928:Thromboxane A2; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester