EXTRACELLULAR ATP IN THE HUMAN KIDNEY - MODE OF RELEASE AND VASCULAR EFFECTS

1 We have previously shown that ATP is a co-transmitter of noradrenali ne in the rat kidney. In the present study the release of ATP and nora drenaline from human kidney cortex was investigated. Vascular effects of ATP and stable analogues were tested in human and rabbit isolated r enal blood vessels. 2 Sympathetic nerve stimulation (20 Hz for 1 min) in human kidney slices released 89 +/- 16 fmol noradrenaline per mg we t weight and 99 +/- 20 fmol ATP per mg wet weight in controls (n = 12) . The Na+ channel blocker tetrodotoxin (1 mu M) abolished ATP and nora drenaline release. 3 In human isolated extrarenal arteries the P-2X-pu rinoceptor agonist beta,gamma-methylene-L-ATP caused almost no constri ctor responses. beta,gamma-methylene-L-ATP induced moderate constricto r responses in intrarenal arteries. In preconstricted human intrarenal arteries ATP induced vasodilation. 4 ATP and the P-2Y-receptor agonis t 2-methyl-thio-ATP (2-MeSATP) dilated preconstricted rabbit renal art eries. The P-2Y-receptor antagonist Reactive Blue 2 (3 mu M) Shifted t he concentration response curves of ATP and 2-MeSATP to the right. 5 I n conclusion, sympathetic nerve stimulation induces the release of ATP and noradrenaline in human renal cortex. ATP activates vasoconstricto ry P-2X- and vasodilatory P-2Y-receptors in human renal blood vessels. The net vascular response to ATP in vivo will depend on the tissue di stribution of these purinoceptors.