Neuropeptide y and ATP interact to control renovascular resistance in the rat

Neuropeptide Y (NPY) and ATP are cotransmitters of norepinephrine (NE). Mod ulation of ATP-mediated purinergic neurotransmission by NPY was investigate d in rat perfused kidney. beta,gamma-Methylene-L-ATP (beta,gamma-mATP; 1.0 to 1.5 mu M, n = 8), NE (0.1 mu M, n = 8), and NPY (0.1 mu M, n = 14) incre ased perfusion pressure by maximally 12 +/- 1, 17 +/- 2, and 9 +/- 1 mmHg, respectively. In the presence of NPY, responses to ATP and NE were dramatic ally enhanced. Renal nerve stimulation in the presence of the alpha-adrenoc eptor antagonist phentolamine (1 mu M) induced presser responses of 54 +/- 5 mmHg (n = 6). alpha-Blockade-resistant responses were abolished by the P2 -purinoceptor blocker suramin (300 mu M) and thus mediated by ATP. Purinerg ic responses were also reduced significantly (50%) by the NPY-YI receptor b locker BIBP 3226 (1 mu M). NPY (0.1 mu M) potentiated purinergic presser re sponses and enhanced ATP release from 0.7 +/- 0.2 to 4.1 +/- 0.9 pmol (n = 4) associated with a significant increase of soluble ATPase activity. All N PY effects were prevented by BIBP 3226. Presser responses to renal nerve st imulation delivered at short time intervals, mimicking enhanced sympathetic drive to the kidney, were not constant but showed a progressive rise, whic h was prevented by BIBP 3226. In this study, it is suggested that purinergi c vasoconstriction in rat kidney depends on concomitantly released NPY. NPY by itself is only a weak vasoconstrictor but acts as a modulator of renal vascular resistance by enhancing the effects of its sympathetic cotransmitt ers, especially during sympathetic overactivity.