The effects of extracellular pH on vasopressin inhibition of ATP-sensitive K+ channels in vascular smooth muscle cells.
BACKGROUND
Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (K(ATP)) 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 K(ATP) channels by AVP.


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


RESULTS
Bath application of AVP significantly inhibited extracellular acidification (pH(o) = 6.5)-induced K(ATP) 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 K(ATP) channel activity at mild (pH(o) = 7.0) and severe (pH(o) = 6.5) extracellular acidification, with IC50 values of 266.7 and 21.4 pM, respectively, but failed to significantly inhibit at normal pH (pH(o) = 7.4) or under alkalosis (pH(o) = 9.0). Augmentation of AVP inhibition of vascular K(ATP) 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 K(ATP) channel activity, and that the inhibitory effects of AVP on vascular K(ATP) channels are enhanced by extracellular acidification via the V1 receptor-protein kinase C cell-signaling pathway. The potent inhibition of vascular K(ATP) channels by AVP under acidic conditions may make it suitable for management of vasodilatory shock.
Department of Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. bass@clin.med.tokushima-u.ac.jp
Takashi
T
Kawano
Katsuya
K
Tanaka
Hossein
H
Nazari
Shuzo
S
Oshita
Akira
A
Takahashi
Yutaka
Y
Nakaya
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D045604:Extracellular Fluid / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D001127:Arginine Vasopressin; D000255:Adenosine Triphosphate