Evidence that in vivo constriction of cerebral arterioles by local application of tert-butyl hydroperoxide is mediated by release of endogenous thromboxane.
Pial arterioles of mice were suffused in situ with tert-butyl hydroperoxide (TBHP). This agent has been reported to stimulate synthesis or release of the constrictor, thromboxane. In the present study we observed pial arterioles by in vivo microscopy. Locally applied TBHP produced dose-dependent constriction, significantly inhibited by each of three drugs: acetylsalicylic acid, OKY-046, and SQ-29548. These drugs are respectively a cyclooxygenase inhibitor, a thromboxane synthetase inhibitor, and a thromboxane receptor blocker. Since each acts by a different mechanism to interfere with thromboxane-mediated responses and each inhibited the contractile response to TBHP, thromboxane appears to be a mediator of this response. Platelet aggregation was not seen after local application of TBHP, and the dwell time of platelets at the site of TBHP application is less than 1 second. Thus, platelets are an unlikely source of the thromboxane mediating the local constriction. It is much more likely that the source of thromboxane is either the wall of the pial vessels or the underlying brain and/or its vessels. These data do not distinguish between the latter two possibilities, but if this suggestion is correct, then the data show for the first time that thromboxane can be released from normal brain and/or brain vessels in amounts sufficient to cause arteriolar constriction.
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D008297:Male; D051379:Mice; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D020122:tert-Butylhydroperoxide
D016861:Cyclooxygenase Inhibitors; D010545:Peroxides; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D020122:tert-Butylhydroperoxide