Neuropeptide Y and the Kidney

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, Y2and 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+-ATPase in proximal tubules via Y2receptors 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 occurs largely independent of the pressure natriuresis mechanisms and is possibly mediated by an extrarenal Y5receptor. Studies with the conversion enzyme inhibitor, ramiprilat, and the bradykinin receptor antagonist, icatibant, indicate that bradykinin at least partly mediates 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.