Peptide hormones and the regulation of sodium excretion.

Abstract

KEY WORDS • peptide hormones • hormone receptors • intracellular messengers glomerular filtration rate • sodium reabsorption • sodium excretion T WENTY years ago, intensive research led to the delineation of the role played by alterations in blood composition in mediating the natriuresis that resulted from the infusion of colloidfree isotonic saline solutions into humans and experimental animals. Results of this research indicated that changes in renal hemodynamics (glomerular filtration rate [GFR], renal blood flow, renal vascular resistance, filtration fraction) and hematocrit and plasma protein concentration occurring in response to saline infusion led to inhibition of tubular sodium reabsorption through changes in hydrostatic and oncotic pressures in the peritubular capillary circulation, the socalled physical factor effects.1 Because of these findings, the view emerged that, regardless of the extrarenal consequences of saline expansion, the natriuresis resulted from strictly intrarenal mechanisms. 2 ' 3 This viewpoint was later strengthened by in vitro studies on isolated perfused rabbit proximal convoluted tubule segments that demonstrated a direct effect of bath protein concentration on fluid transport. 4Subsequent research, however, has indicated that the regulation of sodium excretion is more complex. The model of saline expansion natriuresis is clearly unphysiological, and although it has provided important insights into mechanisms regulating tubular sodium reabsorption, their relevance to the day-to-day maintenance of salt balance through changes in sodium excretion may be questioned. Moreover, recent theoretical considerations have drawn attention to the dif-

Opioid Mechanisms Controlling Renal Function

“…While endogenous opioids mediate antinatriuretic responses under these conditions, it appears that, under certain conditions, opioid systems may interact with mechanisms that enhance the renal excretion of sodium. For instance, Humphreys and Lin (1988) have shown that y-melanocyte stimulating hormone, a peptide derived from the 0-endorphin precursor molecule pro-opiomelanocortin, is released from the pituitary during acute unilateral nephrectomy and produces a natriuresis in the remaining contralateral kidney. A role for central endogenous opioids in this renal response was suggested because centrally administered naloxone blocks the reflex natriuresis after acute unilateral nephrectomy (Lin & Humphreys 1985).…”

Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones

“…They exist in a, b and g primary structures, which share a core heptapeptide sequence of amino acids [1][2][3]. Although highly conserved among mammalian species, the functions of these peptides remained elusive until the identification in recent years of a family of five melanocortin receptors (MC1-R-MC5-R), which mediate their cellular actions [4][5][6].…”

Comparison of the Effects on Urinary Sodium Excretion of Indomethacin and of Carbidopa in normal Volunteers given an Intravenous Saline Infusion

“…Various mechanisms, neural [l], circulatory [2] and humoral [3], have been proposed to explain the natriuresis occurring after intravenous (i.v.) infusion of sodium (Na+) chloride.…”