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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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References

1.Nishio, K, Akai, Y, Murao, Y et al. Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock. Crit Care Med 1997; 25: 953–957.CrossRefGoogle ScholarPubMed
2.Kojima, H, Tsujimoto, T, Uemura, M et al. Significance of increased plasma adrenomedullin concentration in patients with cirrhosis. J Hepatol 1998; 28: 840–846.CrossRefGoogle ScholarPubMed
3.Nishikimi, T, Hayashi, Y, Iribu, G et al. Increased plasma adrenomedullin concentrations during cardiac surgery. Clin Sci (Lond) 1998; 94: 585–590.CrossRefGoogle ScholarPubMed
4.Jougasaki, M, Wei, CM, McKinley, LJ, JrBurnett, JC. Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation 1995; 92: 286–289.CrossRefGoogle ScholarPubMed
5.Kobayashi, K, Kitamura, K, Hirayama, N et al. Increased plasma adrenomedullin in acute myocardial infarction. Am Heart J 1996; 131: 676–680.CrossRefGoogle ScholarPubMed
6.Ishimitsu, T, Nishikimi, T, Saito, Y et al. Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. J Clin Invest 1994; 94: 2158–2161.CrossRefGoogle ScholarPubMed
7.Kitamura, K, Kangawa, K, Kawamoto, M et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 1993; 192: 553–560.CrossRefGoogle ScholarPubMed
8.Hinson, JP, Kapas, S, Smith, DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev 2000; 21: 138–167.Google ScholarPubMed
9.Lin, B, Gao, Y, Chang, JK et al. An adrenomedullin fragment retains the systemic vasodepressor activity of rat adrenomedullin. Eur J Pharmacol 1994; 260: 1–4.CrossRefGoogle ScholarPubMed
10.Coppock, HA, Owji, AA, Bloom, SR, Smith, DM. A rat skeletal muscle cell line (L6) expresses specific adrenomedullin binding sites but activates adenylate cyclase via calcitonin gene-related peptide receptors. Biochem J 1996; 318: 241–245.CrossRefGoogle ScholarPubMed
11.Nandha, KA, Taylor, GM, Smith, DM et al. Specific adrenomedullin binding sites and hypotension in the rat systemic vascular bed. Regul Pept 1996; 62: 145–151.CrossRefGoogle ScholarPubMed
12.Miura, K, Ebara, T, Okumura, M et al. Attenuation of adrenomedullin-induced renal vasodilatation by NG-nitro L-arginine but not glibenclamide. Br J Pharmacol 1995; 115: 917–924.CrossRefGoogle Scholar
13.Yoshikawa, D, Kuroda, M, Tsukagoshi, H et al. The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats. Anesth Analg 2003; 96: 125–131.CrossRefGoogle ScholarPubMed
14.Kuroda, M, Yoshikawa, D, Nishikawa, K et al. Volatile anesthetics inhibit calcitonin gene-related peptide receptor-mediated responses in pithed rats and human neuroblastoma cells. J Pharmacol Exp Ther 2004; 311: 1016–1022.CrossRefGoogle ScholarPubMed
15.Gray, GA, Furman, BL, Parratt, JR. Endotoxin-induced impairment of vascular reactivity in the pithed rat: role of arachidonic acid metabolites. Circ Shock 1990; 31: 395–406.Google ScholarPubMed
16.Shiga, T, Yoshikawa, D. Platelet-activating factor-induced loss of vascular responsiveness to noradrenaline in pithed rats: involvement of nitric oxide. Eur J Pharmacol 1995; 282: 151–156.CrossRefGoogle ScholarPubMed
17.Yoshikawa, D, Shiga, T, Saito, S et al. Platelet-activating factor receptor antagonist attenuates endotoxin-induced vascular hyporeactivity in the pithed rat. Eur J Pharmacol 1998; 342: 241–245.CrossRefGoogle ScholarPubMed
18.Saxena, PR, Villalon, CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol 1990; 15: 17–34.CrossRefGoogle ScholarPubMed
19.Brain, SD, Grant, AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev 2004; 84: 903–934.CrossRefGoogle ScholarPubMed
20.Ihara, T, Ikeda, U, Tate, Y et al. Positive inotropic effects of adrenomedullin on rat papillary muscle. Eur J Pharmacol 2000; 390: 167–172.CrossRefGoogle ScholarPubMed
21.Lambert, DG. Signal transduction: G proteins and second messengers. Br J Anaesth 1993; 71: 86–95.CrossRefGoogle ScholarPubMed
22.Tanaka, S, Tsuchida, H. Effects of halothane and isoflurane on beta-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta. Anesthesiology 1998; 89: 1209–1217.CrossRefGoogle ScholarPubMed
23.Franks, NP, Lieb, WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367: 607–614.CrossRefGoogle ScholarPubMed
24.Streiff, J, Jones, K, Perkins, WJ et al. Effect of halothane on the guanosine 5′ triphosphate binding activity of G-protein alphai subunits. Anesthesiology 2003; 99: 105–111.CrossRefGoogle ScholarPubMed