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The effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats

Published online by Cambridge University Press:  01 July 2008

M. Kuroda ,
D. Yoshikawa ,
S. Koizuka ,
K. Nishikawa ,
S. Saito  and
F. Goto
M. Kuroda*
Affiliation:
Gunma University Graduate School of Medicine, Department of Anaesthesiology, Maebashi, Japan
D. Yoshikawa
Affiliation:
Isesaki Municipal Hospital, Department of Anaesthesiology, Isesaki, Japan
S. Koizuka
Affiliation:
Gunma University Graduate School of Medicine, Department of Anaesthesiology, Maebashi, Japan
K. Nishikawa
Affiliation:
Gunma University Graduate School of Medicine, Department of Anaesthesiology, Maebashi, Japan
S. Saito
Affiliation:
Gunma University Graduate School of Medicine, Department of Anaesthesiology, Maebashi, Japan
F. Goto
Affiliation:
Gunma University Graduate School of Medicine, Department of Anaesthesiology, Maebashi, Japan
*
Department of Anaesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan. E-mail: [email protected]; Tel: +81 27 220 8454; Fax: +81 27 220 8473
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Summary

Background and objectives

Adrenomedullin is a potent vasodilatory peptide. The mechanisms of adrenomedullin-induced responses are via guanine nucleotide guanosine 5′-triphosphate-binding protein (G-protein)-coupled receptor activation and are similar to those of calcitonin gene-related peptide (CGRP). Previously, we reported that sevoflurane and isoflurane inhibit CGRP-induced haemodynamic responses. The effects of volatile anaesthetics on adrenomedullin-induced haemodynamic responses, however, are unclear. We hypothesized that the volatile anaesthetic isoflurane inhibits adrenomedullin-induced haemodynamic responses. We studied the effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats, which enables us to evaluate the direct cardiovascular effects of drugs without interference from centrally mediated circulatory reflexes.

Methods

Male Wistar rats were pithed by inserting a stainless-steel rod into the spinal cord. Following median sternotomy, a flow probe was placed around the ascending aorta to measure aortic blood flow. Mean arterial pressure and cardiac output were maintained at approximately 100 mmHg and 50 mL min−1, respectively, with continuous infusion of norepinephrine. After 30 min inhalation of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or 30 μg kg−1) was administered intravenously.

Results

Adrenomedullin administration induced a transient increase followed by a persistent decrease in mean arterial pressure and cardiac output. Isoflurane (2%) significantly inhibited the initial increase in mean arterial pressure and the later decrease in mean arterial pressure and systemic vascular resistance.

Conclusion

Isoflurane inhibits adrenomedullin-induced vasodilation and positive inotropic effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor-mediated response, which is a common pathway for both actions.

Keywords

ADRENOMEDULLINISOFLURANECARDIOVASCULAR PHYSIOLOGIC PHENOMENARAT, pithed
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 7 , July 2008 , pp. 544 - 549
Copyright
Copyright © European Society of Anaesthesiology 2008

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