Submitted on April 26, 2007
Accepted on October 6, 2007
ADENOSINE TRIPHOSPHATE (ATP) INCREASES THE REACTIVITY OF THE AFFERENT ARTERIOLE TO LOW CONCENTRATIONS OF NOREPINEPHRINE
Michael Hultstrom1*, En Yin Lai1, Zufu Ma1, Orjan Kallskog1, Andreas Patzak2, and A. Erik G. Persson3
1 Department of Medical Cell Biology, Division of Physiology, Uppsala University, Uppsala, Sweden
2 Johannes-Muller-Institute of Physiology, University Hospital Charite, Humboldt-University of Berlin, Berlin, Germany
3 Medical Cell Biology, Uppsala University, Uppsala, Sweden
* To whom correspondence should be addressed. E-mail: michael.hultstrom{at}mcb.uu.se.
Introduction: 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.
Methods: 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 both by use of specific agonists and antagonists. Cytosolic calcium was measured using the fluorescent calcium dye Fura-2.
Results: 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, respectively) 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 10-7 mol/L NE. The P2-type ATP receptor blocker 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.
Conclusion: Co-stimulation 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.
