Abstract
Afferent arteriolar myogenic and tubuloglomerular feedback responses are critical for the proper maintenance of renal hemodynamics and water and electrolyte homeostasis. Adenosine triphosphate (ATP) P2X receptor activation and 20-hydroxyeicosatetraenoic acids (20-HETE) have been implicated in afferent arteriolar autoregulatory responses. Besides these two participants, members of the degenerin/epithelial Na+ channel (DEG/ENaC) family have been demonstrated to play a pivotal role in the afferent arteriolar myogenic response. The aim of this study was to determine if ENaC contributes to P2X receptor- or 20-HETE-mediated afferent arteriolar vasoconstriction. As previously demonstrated, afferent arteriolar diameter responses to increasing perfusion pressure from 100 to 160 mmHg were abolished by ENaC inhibitors amiloride or benzamil. Afferent arteriolar diameter decreased by 29% under control conditions and by 1% and 5% in the presence of amiloride or benzamil, respectively. The P2X receptor agonist β,γ-methylene ATP decreased afferent arteriolar diameter by 3 ± 1%, 7 ± 1%, 12 ± 2%, and 17 ± 3% in response to 0.1, 1, 10, and 100 μmol/L, respectively. ENaC inhibition did not alter the afferent arteriolar vasoconstrictor response to the P2X receptor agonist β,γ-methylene ATP. Like P2X receptor activation, 20-HETE dose-dependently decreased afferent arteriolar diameter and this vasoconstrictor response was not altered by the presence of ENaC inhibitors amiloride or benzamil. These results suggest that DEG/ENaC channels are required for afferent arteriolar autoregulatory responses; however, DEG/ENaC channels do not contribute to P2X receptor- or 20-HETE-mediated afferent arteriolar vasoconstriction.
Highlights
Renal blood flow and glomerular filtration rate are tightly regulated at a constant level in the face of changing perfusion pressures to properly maintain whole body water and electrolyte balance (Loutzenhiser et al 2006; Inscho 2009)
We previously demonstrated that 20-hydroxyeicosatetraenoic acids (20-HETE) contributed to Adenosine triphosphate (ATP) P2X receptormediated afferent arteriolar vasoconstriction (Zhao et al 2001)
This study determined if ENaC participates in the afferent arteriolar vasoconstrictor response to P2X receptor activation or 20-HETE
Summary
Renal blood flow and glomerular filtration rate are tightly regulated at a constant level in the face of changing perfusion pressures to properly maintain whole body water and electrolyte balance (Loutzenhiser et al 2006; Inscho 2009). This autoregulation of renal blood flow and glomerular filtration rate is impaired in disease states such as hypertension and diabetes (Griffin and Bidani 2004). This simple phenomenon was observed many decades ago, but underlying vascular smooth muscle cell-signaling mechanisms are not fully understood
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