Substance P decreases fluid absorption in the renal proximal tubule

Substance P is a neuropeptide found principally in the central nervous system and peripheral afferent nerve fibers. It is widely distributed in the body, and its local release is thought to have important effects in the normal physiology and pathophysiology of several organ systems. Substance P releases histamine from mast cells and nitric oxide from endothelial cells. Systemic infusion of substance P causes a brisk natriuresis. Previously, proximal tubule transport in the kidney was measured in vivo during the infusion of substance P. Transport was inhibited. This could have been a direct action of substance P or secondary to the release of histamine or nitric oxide. Therefore, we have now studied the effect of substance P on isolated proximal tubules perfused in vitro. We found that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption in rabbit proximal straight tubule. This effect was reversible on removal of substance P from the bath. Inhibition of nitric oxide production with NG-monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at 10(-10) M. The sensitivity of the proximal tubule to low concentrations of substance P, together with the recent findings of substance P-containing afferent fibers within the cortex of the kidney, suggest a role for substance P in the control of proximal tubule reabsorption, particularly in pathophysiological conditions associated with increased afferent nerve activity, such as ureteric occlusion.