Angiotensin II‐adenosine interaction via receptors and intracellular calcium in afferent arterioles

Abstract

Adenosine and angiotensin II (Ang II) interact in the control of renal blood perfusion and glomerular filtration rate. Here we test the hypothesis that Ang II in low concentrations enhances adenosine vasoconstrictor effects. Further, we investigated cytosolic calcium transients and the role of adenosine and Ang II receptors in this context. Bolus application of Ang II (10−12 and 10−10mol/l) induced negligible vasoconstrictions in isolated perfused afferent arterioles of mice, while Ang II 10−8mol/l reduced diameters by about 35% within 2 min. The arteriolar response to cumulative adenosine applications (10−11 to 10−4 mol/l) was very small, but clearly enhanced by Ang II at 10−12,10−10, 10−8 mol/l, respectively. In Fura‐2 AM loaded arterioles, adenosine bolus application induced an increase of the calcium concentration in the arteriolar wall which was greater at 10−5 mol/l compared with 10−8 mol/l. Ang II (10−11 to 10−6 mol/l) induced a concentration dependent increase of cytosolic calcium concentration. Ang II receptor type 1 (AT1AR) antagonist ZD7155 (10−7 mol/l) nearly prevented this Ang II effect. Simultaneous application of Ang II enhanced the calcium concentration to 10−8 and 10−5 mol/l adenosine. The results show that Ang II enhances adenosine induced vasoconstriction even at low concentrations and that this effect goes along with increased calcium transients.