Renal effects of neuropeptide Y

Abstract

 Neuropeptide Y (NPY) is a co-transmitter of the sympathetic nervous system including the renal nerves. The kidney expresses NPY receptors, which can also be activated by peptide YY (PYY), a circulating hormone released from gastrointestinal cells. Five subtypes of NPY receptors have been cloned, among which Y₁, Y₂ and Y₅ appear to be involved in the regulation of renal function. NPY produces potent renal vasoconstriction in vitro in isolated interlobar arteries and in the isolated perfused kidney and in vivo upon intrarenal or systemic administration via a Y₁ receptor. Nevertheless glomerular filtration rate is altered only little if at all by NPY, indicating a greater effect on the vas efferens than the vas afferens. NPY can inhibit renin release via Y₁-like receptors. NPY can stimulate Na⁺/K⁺ adenosine triphosphatase (Na⁺/K⁺-ATPase) in proximal tubules via Y₂ receptors and can antagonize the effects of vasopressin on isolated collecting ducts. It can also act prejunctionally to inhibit noradrenaline release via Y₂ receptors. Despite the profound reductions of renal blood flow, systemic NPY infusion can cause diuresis and natriuresis; this is largely independent of pressure natriuresis mechanisms and is possibly mediated by an extrarenal Y₅ receptor. Studies with the converting enzyme inhibitor ramiprilat and the bradykinin receptor antagonist icatibant indicate that bradykinin mediates, at least partly, diuretic NPY effects. NPY antagonists enhance basal renal blood flow but do not alter basal diuresis or natriuresis indicating that renovascular, but not tubular, NPY receptors may be tonically activated by endogenous NPY.