Release of endothelium-derived relaxing factor after subarachnoid hemorrhage

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✓ The purpose of this study was to determine the cause of the loss of endothelium-dependent relaxation observed in chronic cerebral vasospasm. A bioassay system was developed to measure the release of endothelium-derived relaxing factor (EDRF) from canine basilar arteries. Subarachnoid hemorrhage (SAH) was induced in dogs by two injections of autologous blood into the cisterna magna. Angiograms were performed on the 7th day after SAH to check the presence of chronic vasospasm. The animals were sacrificed on the 8th day, and in vitro experiments were performed on rings harvested from the basilar artery. These confirmed loss of endothelium-dependent relaxation in response to bradykinin and arginine vasopressin in the group with SAH. The basilar arteries were perfused with modified Krebs-Ringer solution. The perfusate was bioassayed with a ring of coronary artery without endothelium (bioassay ring). The release of the EDRF was detected by relaxation of the bioassay ring contracted with prostaglandin F2α. Arginine vasopressin and bradykinin added to the perfusate upstream of the basilar artery caused concentration-dependent release of the EDRF. The direct effect of these peptides on the smooth muscle of the bioassay ring was to cause contraction. The release of the EDRF was identical in basilar arteries from the control and the SAH groups. These results indicate that the release of the EDRF is not impaired during chronic vasospasm, and thus that the loss of the endothelium-dependent relaxation is due to a decreased transfer of the EDRF or a reduced responsiveness of the smooth muscle to the factor.

Article Information

Address reprint requests to: Paul M. Vanhoutte, M.D., Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.

© AANS, except where prohibited by US copyright law.

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Figures

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    Schematic illustration of the bioassay system for analysis of endothelium-derived relaxing factor released from the basilar artery. See text for the measuring procedure.

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    Concentration-response curves to arginine vasopressin (left) and bradykinin (right) of basilar artery rings with endothelium in the absence and presence of indomethacin. The rings were contracted with uridine 5′-triphosphate (3 × 10−6 M). Responses are expressed as percent of the maximal relaxation of each ring to papaverine (10−4 M). Data shown are the mean ± standard error of the mean.

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    Concentration-response curves to arginine vasopressin (left) and bradykinin (right) of basilar artery rings without endothelium in the absence of indomethacin. The rings were contracted with uridine 5′-triphosphate (3 × 10−6 M). Responses are expressed as percent of the maximal relaxation of each ring to papaverine (10−4 M). Data shown are the mean ± standard error of the mean in four animals.

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    An example of recording during a bioassay experiment. A coronary artery ring without endothelium (bioassay ring) was contracted with prostaglandin F2α (4 × 10−6 M). When the contraction reached plateau, arginine vasopressin was given during direct superfusion. After the perfusion was switched to the arterial line (endothelial superfusion), arginine vasopressin was added to the perfusate upstream of the basilar artery.

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    Graphs showing the effect of increasing concentrations of arginine vasopressin (left) and bradykinin (right) on the release of endothelium-derived relaxing factor from canine basilar arteries studied under bioassay conditions. The relaxations of the bioassay coronary artery ring are expressed as percent of their response to sodium nitroprusside (10”6 M). Data shown are the mean ± standard error of the mean for seven dogs.

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    Subtracted responses of the release of endothelium-derived relaxing factor. The relaxation of the bioassay ring observed during arterial perfusion with arginine vasopressin (10−7 M, left) and bradykinin (10−6 M, right) was subtracted from the contractions (positive value) observed during direct perfusion with the same concentration of the agonists. The responses are expressed as the percent of relaxation induced by sodium nitroprusside (10−6 M). Responses shown are the mean ± standard error of the mean for seven animals.

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