Endogenous endothelin and vasopressin support blood pressure during epidural anesthesia in conscious dogs.
We studied whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during high epidural anesthesia when efferent sympathetic drive is diminished. On different days, six awake dogs underwent each of the following five interventions: blockade of vasopressin V(1a) receptors using [d(CH(2))(5)Tyr(Me(2))]AVP, (40 microg/kg) or endothelin receptors using tezosentan (3 mg/kg followed by 3 mg. kg(-1). h(-1)) with or without epidural anesthesia (1% lidocaine, intraindividual dose did not differ between experiments), and epidural saline (n = 5). The effects of endothelin- or vasopressin-receptor blockade were analyzed (means +/- SEM) and compared by an analysis of variance for repeated measures (paired Student's t-test, alpha-adjusted, P < 0.05). Vasopressin-receptor blockade decreased blood pressure (10 +/- 2 mm Hg) only in the presence of epidural anesthesia, whereas endothelin-receptor blockade reduced blood pressure both in the presence and absence of epidural anesthesia (12 +/- 3 versus 10 +/- 1 mm Hg). During baseline and each intervention, plasma concentrations of vasopressin and big-endothelin were measured and compared by a Wilcoxon's rank sum test; P < 0.05. Vasopressin concentrations increased during epidural anesthesia and after additional endothelin receptor blockade, but big-endothelin concentrations remained unchanged during each intervention. We conclude that vasopressin acts as a reserve system, as it stabilizes blood pressure specifically during epidural anesthesia, whereas the unchanged concentrations of big-endothelin indicate that the endothelin system is not specifically activated to support blood pressure during epidural anesthesia.


CONCLUSIONS
We studied in awake dogs whether endogenous endothelin, like endogenous vasopressin, helps to maintain blood pressure during resting conditions and epidural anesthesia. Only vasopressin was specifically activated to support blood pressure during epidural anesthesia, whereas endothelin supported blood pressure to the same extent during epidural anesthesia and during resting conditions.
Picker
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Department of Anesthesiology, Heinrich-Heine-University, Duesseldorf, Germany. olaf.picker@uni-duesseldorf.de
Schindler
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AW
Scheeren
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TW
D000767:Anesthesia, Epidural; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects; D017483:Receptors, Vasopressin / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D014667:Vasopressins / Q000097:blood / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006727:Hormone Antagonists; D011725:Pyridines; D017466:Receptors, Endothelin; D017483:Receptors, Vasopressin; D013777:Tetrazoles; D014667:Vasopressins; D001127:Arginine Vasopressin; C120582:tezosentan; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-