Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries

Abstract

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.

Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage

“…However, ET-1 concentrations in CSF and plasma are in the picomolar range, levels unlikely to be capable of causing significant contraction. 27 Most of the ET would be released locally and, therefore, would not reach the systemic circulation, thus yielding local concentrations of immunoreactive ET much higher at the vascular endothelium-smooth muscle interface than in the blood stream. 2,32,46,49,62 Endothelin should be regarded more as a paracrine than as an endocrine hormone.…”

“…32,35,52,59,65 Both intra-and extraluminal ET have displayed potent and dose-dependent vasoconstricting effects on basilar arteries. 27 The effects of intraluminal (but not extraluminal) ET was enhanced by extraluminal oxyHb and N G -monomethyl-L-arginine, an inhibitor of endothelial NO syn- Tables 1 and 2 for classifications of phases and hypodense area groups. Vasospasm was estimated on the basis of postoperative angiograms obtained within 5 to 14 days post-SAH.…”

Evaluation of big endothelin–1 concentrations in serum and ventricular cerebrospinal fluid after early surgical compared with nonsurgical management of ruptured intracranial aneurysms

“…In the clinical setting of aneurysmal SAH, synthesis of ETs may be stimulated by several substances present in the subarachnoid blood clot, such as oxyhemoglobin, 27,28,37 thrombin, 30 and transforming growth factor ␤-1. 33 In the "endothelin hypothesis" it is suggested that an abluminal clot stimulates vascular endothelium to produce ETs and that ET-1 and its intermediate precursor, big ET-1, are among the factors inducing the prolonged vasoconstriction of vasospasm.…”

“…33 In the "endothelin hypothesis" it is suggested that an abluminal clot stimulates vascular endothelium to produce ETs and that ET-1 and its intermediate precursor, big ET-1, are among the factors inducing the prolonged vasoconstriction of vasospasm. 27,28,31,37,48,50 Studies in which elevated post-SAH serum and CSF ET concentrations are reported are usually performed in patients undergoing neurosurgical operations, such as craniotomy and clipping of the ruptured aneurysm. 12,36,42,44 The influence of such major surgical interventions on ET levels is unknown.…”

Endothelin-1 and cerebral blood flow in a porcine model

“…They found a statistically significantly greater effect (p < 0.01) of ET on the basilar arteries than on the femoral or mesenteric arteries. 31 However, this problem remains to be elucidated in further investigations.…”