Release and vasoconstrictor effects of neuropeptide Y in relation to non-adrenergic sympathetic control of renal blood flow in the pig.
The possible involvement of neuropeptide Y (NPY) in sympathetic control of renal blood flow was investigated in the pig in vivo. Exogenous NPY caused renal vasoconstriction with a threshold effect at an arterial plasma concentration of 164 pmol 6(-1). Stimulation of the renal nerves (0.59, 2 and 10 Hz) in control animals evoked rapid and frequency-dependent reduction in renal blood flow and overflow of NPY-like immunoreactivity (NPY-LI) and noradrenaline (NA) from the kidney, suggesting co-release from sympathetic nerves. Following the administration of the alpha- and beta-adrenoceptor antagonists phenoxybenzamine and propranolol, the vasoconstrictor response to exogenous NA was reduced by 98%, whereas that of NPY was unaltered. The response to nerve stimulation with 0.59 Hz was abolished, whereas relatively slowly developing reductions in renal blood flow by 7 and 28% were obtained upon stimulation with 2 and 10 Hz respectively. The nerve stimulation-evoked overflow of NA at 0.59 and 2 Hz, but not at 10 Hz and not that of NPY-LI, was enhanced after adrenoceptor blockade. Twenty-four hours after reserpine treatment (1 mg kg-1 i.v.) the contents of NPY-LI and NA in the renal cortex were reduced by 80 and 98% respectively. Sectioning of the renal nerves largely prevented the reserpine-induced depletion of NPY-LI, but not that of NA. Nerve stimulation of the denervated kidney with 2 and 10 Hz 24 h after reserpine treatment evoked slowly developing and long-lasting reductions in renal blood flow by 6 and 52% respectively. These responses were associated with overflow of NPY-LI, which was similar to and threefold higher than that observed in controls at 2 and 10 Hz respectively, while no detectable overflow of NA occurred. Repeated stimulation with 10 Hz resulted in a progressive fatigue of the vasoconstrictor response and the associated overflow of NPY-LI, giving a high correlation (r = 0.86, P less than 0.001) between the two parameters. It is concluded that NPY is a potent constrictor of the renal vascular bed. Furthermore, although NA is the likely transmitter mediating most of the responses to low to moderate nerve activation under control conditions, the data suggest that NPY may mediate the non-adrenergic reductions in renal blood flow evoked by high-frequency sympathetic nerve stimulation after reserpine treatment.
Pernow
J
J
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D007668:Kidney / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009478:Neuropeptide Y; D012110:Reserpine; D009638:Norepinephrine