Previous studies have indicated that 20-hydroxyeicosatetraeonic
acid (20-HETE) modulates vascular tone in large cerebral and renal arteries through inhibition of the large conductance,
calcium sensitive
potassium (
BK) channel activity. However, the role of
20-HETE in modulating tubuloglomerular feedback (TGF) and the myogenic response in the afferent arteriole (Af-Art) is unknown. The present study examined the effects of inhibitors of the synthesis and action of
20-HETE on the myogenic and TGF responses of isolated rabbit and mouse Af-Arts.
Luminal diameter decreased by 9.2±0.5% in mice and 8.9±1.3% in rabbit Af-Art when the perfusion pressure was increased from 60 to 120 mmHg. Administration of a
20-HETE synthesis inhibitor,
HET0016 (1 μM), or a selective
20-HETE antagonist, 6, 15-20-hydroxyeicosadienoic
acid (6, 15-20-HEDE, 10 μM) completely blocked the myogenic response of both rabbit and mouse Af-Art, while addition of 5, 14-20-HEDE (10 μM), a
20-HETE agonist, restored the myogenic response in vessels treated with
HET0016. Increases in NaCl concentration from 10 to 80 mM of the
solution perfusing the macula densa constricted the Af-Art of rabbits by 6.0±1.4 μm (n=5). Addition of a
20-HETE agonist to the tubular perfusate potentiated the TGF-mediated
vasoconstrictor response. This response was blocked by addition of a
20-HETE antagonist (6, 15-20-HEDE, 10 μM) to the vascular perfusate. These studies indicate that locally produced
20-HETE plays an important role in modulating the myogenic and TGF responsiveness of the Af-Art and may help explain how deficiencies in the renal formation of
20-HETE could promote the development of
hypertension induced glomerular injury.