TY - JOUR
T1 - Glomerular stereospecific synthesis and hemodynamic actions of 8,9-epoxyeicosatrienoic acid in rat kidney
AU - Katoh, Tetsuo
AU - Takahashi, Kihito
AU - Capdevila, Jorge
AU - Karara, Armando
AU - Falck, J R
AU - Jacobson, Harry R.
AU - Badr, Kamal F.
PY - 1991
Y1 - 1991
N2 - Renal glomerular and cortical metabolism of endogenous arachidonic acid by cytochrome P-450 epoxygenase yields 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EET). Using gas chromatography-mass spectrometry, we measured the synthesis of 8,9-EET from an endogenous pool of arachidonic acid in normal rat kidney. The (8S,9R) isomer was favored over the (8R,9S) isomer in a ratio (%) of 59 to 41 in isolated glomeruli and 68 to 32 in cortex tissue. (8S,9R)- but not (8R,9S)-EET elicited dose-dependent vasoconstriction on intrarenal administration in the euvolemic Munich-Wistar rat. Micropuncture measurements of glomerular dynamics revealed that (8S,9R)-EET increased afferent arteriolar resistance (R(A)) leading to reductions in single-nephron plasma flow rate (Q̇(A)), net transcapillary hydraulic pressure difference (ΔP), and consequently single-nephron glomerular filtration rate (SNGFR). There was no significant change in the value of the glomerular capillary ultrafiltration coefficient (K(f)). In the presence of a cyclooxygenase inhibitor, indomethacin, the effects of 8,9-EET were reversed. R(A) fell leading to increases in Q̇(A) and ΔP, with resultant angmentation of SNGFR. Under these conditions, a modest reduction if K(f) was noted. Thus (8S,9R)-EET is a stereoselective renal vasoconstrictor, preferentially generated over its optical isomer, (8R,9S)-EET, suggesting that it is biologically relevant and implying specific structural requirements for EET receptor activation. The principal mechanism of action of 8,9-EET is preglomerular vasoconstriction. The vasoconstrictor effect of 8,9-EET is CO dependent.
AB - Renal glomerular and cortical metabolism of endogenous arachidonic acid by cytochrome P-450 epoxygenase yields 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EET). Using gas chromatography-mass spectrometry, we measured the synthesis of 8,9-EET from an endogenous pool of arachidonic acid in normal rat kidney. The (8S,9R) isomer was favored over the (8R,9S) isomer in a ratio (%) of 59 to 41 in isolated glomeruli and 68 to 32 in cortex tissue. (8S,9R)- but not (8R,9S)-EET elicited dose-dependent vasoconstriction on intrarenal administration in the euvolemic Munich-Wistar rat. Micropuncture measurements of glomerular dynamics revealed that (8S,9R)-EET increased afferent arteriolar resistance (R(A)) leading to reductions in single-nephron plasma flow rate (Q̇(A)), net transcapillary hydraulic pressure difference (ΔP), and consequently single-nephron glomerular filtration rate (SNGFR). There was no significant change in the value of the glomerular capillary ultrafiltration coefficient (K(f)). In the presence of a cyclooxygenase inhibitor, indomethacin, the effects of 8,9-EET were reversed. R(A) fell leading to increases in Q̇(A) and ΔP, with resultant angmentation of SNGFR. Under these conditions, a modest reduction if K(f) was noted. Thus (8S,9R)-EET is a stereoselective renal vasoconstrictor, preferentially generated over its optical isomer, (8R,9S)-EET, suggesting that it is biologically relevant and implying specific structural requirements for EET receptor activation. The principal mechanism of action of 8,9-EET is preglomerular vasoconstriction. The vasoconstrictor effect of 8,9-EET is CO dependent.
KW - cyclooxygenase
KW - eicosanoids
KW - glomerular filtration
KW - renal blood flow
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U2 - 10.1152/ajprenal.1991.261.4.f578
DO - 10.1152/ajprenal.1991.261.4.f578
M3 - Article
C2 - 1928373
AN - SCOPUS:0025990867
VL - 261
SP - F578-F586
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 4 30-4
ER -