The role of nitric oxide in pericyte‐mediated regulation of vasa recta diameter

Abstract

Pericytes are known to regulate vasa recta diameter in response to many different vasoactive agents endogenous to the kidney [1]. Nitric oxide (NO) signaling pathways are important in the renal medulla for regulation of blood flow and natriuresis. Here we use the live kidney slice model to characterize the mechanisms by which NO regulates pericyte‐mediated control of vasa recta diameter and thus medullary blood flow (MBF).Kidney slices (200 μm thick) were obtained from adult, male rats as previously described [1]. Kidney slices were superfused with agents that manipulate endogenous NO signaling pathways: L‐NAME [an inhibitor of nitric oxide synthase (NOS)], or L‐VNIO (a NOS1‐specific inhibitor), or SNAP (a NO donor). DIC video imaging techniques were used to record real‐time changes in vasa recta diameter, in response to bath application of these compounds. SNAP (100 μM) caused a significant dilation of vasa recta specifically at pericyte sites (12.6±2.9% p<0.05 n=15). L‐NAME (1 mM) and L‐VNIO (1 μM) each caused vasoconstriction significantly greater at pericyte sites compared with non‐pericyte sites (8.6±1.1% p<0.05 n=13 and 10.8±2.0% p<0.05 n=6, respectively).Here we demonstrate that NO derived from NOS1 specifically is key in pericyte‐mediated regulation of vasa recta diameter, and thus renal MBF.Research supported by the Medical Research Council