High Salt Diet Attenuates Juxtamedullary Afferent Arteriolar Autoregulatory Behavior and Responsiveness to P2X1 Receptor Stimulation

Abstract

High salt diet reduces myogenic reactivity in resistance vessels. P2 receptors are important for intact afferent arteriolar (AA) autoregulation. We tested the hypothesis that AA autoregulation and responsiveness to P2 receptor activation is impaired in rats fed an 8% NaCl diet (HS) for 14 days. AA responses to β, γ‐methylene ATP, a P2X1 receptor agonist (0.01, 0.1, 1, 10 and 100 μM) were determined in kidneys perfused at 100 mmHg. Autoregulatory behavior was determined in 15 mmHg increments from 65 to 170 mmHg. Systolic blood pressure increased slightly from a baseline of 107±2 mmHg to 115 ± 2 mmHg after 14 days on a HS diet (P < 0.05; n = 34). In control kidneys from normal salt rats (NS), AA diameter decreased by 37 ± 2% (n=4) as perfusion pressure increased from 65 to 170 mmHg. In the HS group AA diameter decreased by 6 ± 4% (P < 0.05; n = 8) indicating marked reduction in pressure mediated vasoconstriction. In NS kidneys, the P2X1 agonist β, γ‐methylene ATP reduced AA diameter by 9 ± 2, 14 ± 8, 18 ± 7, 21 ± 9 and 28 ± 11% (n = 3). In HS kidneys, responses to β, γ‐methylene ATP were markedly impaired. AA diameter decreased by 0 ± 2, 3 ± 4, 4 ± 4, 7 ± 4 and 11 ± 4%, respectively (P < 0.05 vs. NS). These data demonstrate that a HS challenge impairs AA autoregulatory behavior. Loss of autoregulatory behavior is associated with impaired responsiveness to P2X1 receptor activation, consistent with P2X receptors mediating autoregulatory behavior. NIH DK44628