Extracellular ATP in the human kidney: mode of release and vascular effects

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Abstract
1. We have previously shown that ATP is a co-transmitter of noradrenaline in the rat kidney. In the present study the release of ATP and noradrenaline from human kidney cortex was investigated. Vascular effects of ATP and stable analogues were tested in human and rabbit isolated renal blood vessels. 2. Sympathetic nerve stimulation (20 Hz for 1 min) in human kidney slices released 89 +/- 16 fmol noradrenaline per mg wet weight and 99 +/- 20 fmol ATP per mg wet weight in controls (n = 12). The Na+ channel blocker tetrodotoxin (1 microM) abolished ATP and noradrenaline release. 3. In human isolated extrarenal arteries the P2X-purinoceptor agonist beta, gamma-methylene-L-ATP caused almost no constrictor responses, beta, gamma-methylene-L-ATP induced moderate constrictor responses in intrarenal arteries. In preconstricted human intrarenal arteries ATP induced vasodilation. 4. ATP and the P2Y-receptor agonist 2-methyl-thio-ATP (2-MeSATP) dilated preconstricted rabbit renal arteries. The P2Y-receptor antagonist Reactive Blue 2 (3 microM) shifted the concentration response curves of ATP and 2-MeSATP to the right. 5. In conclusion, sympathetic nerve stimulation induces the release of ATP and noradrenaline in human renal cortex. ATP activates vasoconstrictory P2X- and vasodilatory P2Y-receptors in human renal blood vessels. The net vascular response to ATP in vivo will depend on the tissue distribution of these purinoceptors.