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Anesth Analg 2007; 105:1714-1719
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000290334.91624.2f
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CRITICAL CARE AND TRAUMA

The Effects of Extracellular pH on Vasopressin Inhibition of ATP-Sensitive K+ Channels in Vascular Smooth Muscle Cells

Takashi Kawano, MD*, Katsuya Tanaka, MD*, Hossein Nazari, PhD{dagger}, Shuzo Oshita, MD*, Akira Takahashi, MD{dagger}, and Yutaka Nakaya, MD{dagger}

From the Departments of *Anesthesiology and {dagger}Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

Address correspondence and reprint requests to Takashi Kawano, MD, Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Address e-mail to bass{at}clin.med.tokushima-u.ac.jp.

BACKGROUND: Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (KATP) channels and may help to restore vascular tone in patients with vasodilatory shock. In the present study, we investigated whether extracellular acidification modifies the inhibition of vascular KATP channels by AVP.

METHODS: We used a cell-attached patch-clamp configuration to investigate the effects of extracellular pH (pHo) on AVP-KATP channel interaction in rat aortic smooth muscle cells.

RESULTS: Bath application of AVP significantly inhibited extracellular acidification (pHo = 6.5)-induced KATP channel activity in a concentration-dependent manner, with an half-maximal inhibitory concentration (IC50) value of 16.8 pM. Furthermore, bath application of AVP significantly inhibited pinacidil-induced KATP channel activity at mild (pHo = 7.0) and severe (pHo = 6.5) extracellular acidification, with IC50 values of 266.7 and 21.4 pM, respectively, but failed to significantly inhibit at normal pH (pHo = 7.4) or under alkalosis (pHo = 9.0). Augmentation of AVP inhibition of vascular KATP channels during extracellular acidification was eliminated by pretreatment with OPC-21268, a specific blocker of the V1 receptor, but not by a V2 blocker, OPC-31260. AVP-induced inhibition was also suppressed by pretreatment with a protein kinase C inhibitor, calphostin C.

CONCLUSIONS: Our results suggest that AVP inhibits extracellular acidification-induced vascular KATP channel activity, and that the inhibitory effects of AVP on vascular KATP channels are enhanced by extracellular acidification via the V1 receptor-protein kinase C cell-signaling pathway. The potent inhibition of vascular KATP channels by AVP under acidic conditions may make it suitable for management of vasodilatory shock.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2007 by the International Anesthesia Research Society.