In the cerebral circulation, endothelin-A receptor activation mediates marked prolonged vasoconstriction whereas endothelin-B (ETB) receptor activation effects dilation. In contrast to some peripheral vascular beds, ET(B) receptor-induced vasoconstriction has not yet been demonstrated in brain vessels. In this study in @entity4486 -anesthetized @entity468 , with perivascular microapplications of ET(B) selective agonist ( @entity18672 ) and antagonist ( @entity11345 ), we investigated whether ET(B) receptor-mediated constriction could be uncovered in cortical arterioles in vivo. In addition, we examined whether normal dilator response to ET(B) receptor activation is preserved in postischemic cerebral arterioles. The first microapplication of the selective ET(B) receptor agonist @entity18672 (1 micromol/L) onto a pial cortical arteriole elicited marked dilation (caliber increased by 26.3 +/- 15.1% from preinjection baseline). A second application of @entity18672 (10-minute interval) onto the same vessel failed to evoke any significant vasomotor response. Subsequent (third and fourth) adventitial microapplication of the ET(B) receptor agonist on the same arteriolar site effected a significant constriction of cerebral arterioles (-15.3 +/- 12.7% and -9.7 +/- 6.3% from preinjection baseline, respectively, at 20 and 30 minutes after the first application). The pial arterioles did not display tachyphylaxis to repeated applications of @entity972 (10 mmol/L). The perivascular application of the ET(B) receptor antagonist @entity11345 (0.001 to 1 micromol/L) had no effect on arteriolar caliber per se but blocked both @entity18672 -induced dilation (inhibitory concentration approximately 5 nmol/L) and vasoconstriction elicited by repeated activation of ET(B) receptors. After @entity2500 , most of the arterioles examined displayed a sustained dilation. The microapplication of @entity18672 into the perivascular space surrounding postischemic dilated arterioles elicited a constriction of a similar magnitude to that induced by application of CSF (-17 +/- 7% and -17 +/- 7% from preinjection baseline, respectively). The adventitial microapplication of the ET(B) receptor antagonist ( @entity11345 , 0.1 micromol/L) on postocclusion dilated pial arterioles effected no change in the arteriolar caliber when compared with preinjection baseline. This @entity11345 -induced response was significantly different from that induced by perivascular microinjection of CSF (P < 0.001, analysis of variance). These investigations indicate that (1) repeated activation of ET(B) receptors displays tachyphylaxis of the vasodilator response but also uncovers significant constriction of cerebral arterioles in vivo; (2) the ability of @entity18672 to elicit dilation is lost within 30 minutes of induced focal @entity63 ; and (3) ET(B)-mediated contractile tone contributes in a small but significant manner in limiting postischemia dilation of cortical pial arterioles.

Endothelin-B receptors in cerebral resistance arterioles and their functional significance after focal cerebral ischemia in XXXX .

@entity18672 :: ('MESH:C075771', 'Chemical') :: ['BQ-3020'] @entity11345 :: ('MESH:C086539', 'Chemical') :: ['BQ-788'] @entity4486 :: ('MESH:D002698', 'Chemical') :: ['chloralose'] @entity2500 :: ('MESH:D020244', 'Disease') :: ['middle cerebral artery occlusion'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity468 :: ('9685', 'Species') :: ['cats']
@entity468 :: (9685,Species) :: ['cats']
