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Am J Physiol Regul Integr Comp Physiol 293: R2225-R2231, 2007. First published October 10, 2007; doi:10.1152/ajpregu.00287.2007
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00287.2007v1
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RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Adenosine triphosphate increases the reactivity of the afferent arteriole to low concentrations of norepinephrine

Michael Hultström,1,* En Yin Lai,1,* Zufu Ma,1 Örjan Källskog,1 Andreas Patzak,2 and A. Erik G. Persson1

1Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden, 2Johannes-Müller-Institute of Physiology, University Hospital Charité, Humboldt-University of Berlin

Submitted 26 April 2007 ; accepted in final form 6 October 2007

Adenosine triphosphate (ATP) and norepinephrine (NE) interact in the control of blood flow in the kidney. A combined effect of NE and ATP has not been previously investigated at the level of the afferent arteriole (Af). We studied the effects of ATP on the contractile response of the Af to NE. Vascular reactivity to ATP, NE, and their combination was investigated in isolated perfused Af from mice. The roles of {alpha}-adrenoceptors and P2-ATP-receptors were investigated by use of specific agonists and antagonists. Cytosolic calcium was measured using the fluorescent calcium dye fura-2. ATP in concentrations from 10–12 to 10–4 mol/l induced transient contractions. NE constricted the Af in a dose-dependent manner and induced significant contractions at > 10–7 mol/l. Treatment with ATP (10–8 and 10–6 mol/l) increased the NE response. Diameters were reduced by 20% already at 10–11 mol/l NE during ATP treatment of 10–6 mol/l. ATP increased the calcium response to NE significantly at 10–8 and 10–7mol/l NE. The P2-type ATP receptor blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (10–5 mol/l) abolished the sensitization of the NE response by ATP. The {alpha}1-blocker prazosin (10–7 mol/l) inhibited the ATP effect, as did the {alpha}2-blocker yohimbine (10–7 mol/l). Neither the phenylephrine- nor clonidine-induced concentration response curves was affected by ATP in the bath solution. Costimulation with ATP enhances the response of the Af to NE. This effect is mediated by increased cytosolic calcium. The enhancing effect involves P2-type ATP receptors and both {alpha}1- and {alpha}2-adrenoceptors.

cytosolic calcium; mice; prazosin; PPADS; renal circulation; yohimbine


Address for reprint requests and other correspondence: M. Hultström, Renal Research Group, Dept. of Internal Medicine, Haukeland Univ. Hospital, Jonas Liesvei 65, 5021 Bergen, Norway (e-mail: michael.hultstrom{at}med.uib.no)






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