TY - JOUR
T1 - Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness
AU - Imig, John D.
AU - Falck, J R
AU - Inscho, Edward W.
PY - 1999
Y1 - 1999
N2 - 1. Previous studies have demonstrated an important role for the cytochrome P450 (CYT-P450) pathway in afferent arteriole autoregulatory responses but the involvement of specific pathways remains unknown. Experiments were performed to determine the role of CYT-P450 epoxygenase and hydroxylase pathways in pressure mediated preglomerular autoregulatory responses. 2. Afferent arteriolar diameter was measured as renal perfusion pressure was increased from 80-160 mmHg. Afferent arteriolar diameter averaged 19 ± 2 μm at a renal perfusion pressure of 80 mmHg and decreased by 15 ± 2% when pressure was increased to 160 mmHg. 3. Inhibition of the epoxygenase pathway with 6-(2-proparglyloxyphenyl)hexanoic acid (PPOH), enhanced the microvascular response to increasing renal perfusion pressure. In the presence of 50 μM PPOH, afferent arteriolar diameter decreased by 29 ± 4% when pressure was increased from 80-160 mmHg. 4. Likewise, the sulphonimide derivative of PPOH, N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (MS-PPOH, 50 μM), enhanced the afferent arteriolar response to increasing renal perfusion pressure. 5. In contrast, the selective CYT-P450 hydroxylase inhibitor, N-methylsulphonyl-12,12-dibromododec-11-enamide (DDMS) attenuated the vascular response to increasing renal perfusion pressure. In the pressure of 25 μM DDMS, afferent arteriolar diameter decreased by 4 ± 2% when pressure was increased from 80-160 mmHg. 6. These results suggest that CYT-P450 metabolites of the epoxygenase pathway alter afferent arteriolar responsiveness and thereby modify the ability of the preglomerular vasculature to autoregulate renal blood flow. Additionally, these results provide further support to the concept that a metabolite of the hydroxylase pathway is an integral component of the afferent arteriolar response to elevations in perfusion pressure.
AB - 1. Previous studies have demonstrated an important role for the cytochrome P450 (CYT-P450) pathway in afferent arteriole autoregulatory responses but the involvement of specific pathways remains unknown. Experiments were performed to determine the role of CYT-P450 epoxygenase and hydroxylase pathways in pressure mediated preglomerular autoregulatory responses. 2. Afferent arteriolar diameter was measured as renal perfusion pressure was increased from 80-160 mmHg. Afferent arteriolar diameter averaged 19 ± 2 μm at a renal perfusion pressure of 80 mmHg and decreased by 15 ± 2% when pressure was increased to 160 mmHg. 3. Inhibition of the epoxygenase pathway with 6-(2-proparglyloxyphenyl)hexanoic acid (PPOH), enhanced the microvascular response to increasing renal perfusion pressure. In the presence of 50 μM PPOH, afferent arteriolar diameter decreased by 29 ± 4% when pressure was increased from 80-160 mmHg. 4. Likewise, the sulphonimide derivative of PPOH, N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (MS-PPOH, 50 μM), enhanced the afferent arteriolar response to increasing renal perfusion pressure. 5. In contrast, the selective CYT-P450 hydroxylase inhibitor, N-methylsulphonyl-12,12-dibromododec-11-enamide (DDMS) attenuated the vascular response to increasing renal perfusion pressure. In the pressure of 25 μM DDMS, afferent arteriolar diameter decreased by 4 ± 2% when pressure was increased from 80-160 mmHg. 6. These results suggest that CYT-P450 metabolites of the epoxygenase pathway alter afferent arteriolar responsiveness and thereby modify the ability of the preglomerular vasculature to autoregulate renal blood flow. Additionally, these results provide further support to the concept that a metabolite of the hydroxylase pathway is an integral component of the afferent arteriolar response to elevations in perfusion pressure.
KW - Autoregulation
KW - Endothelium-derived hyperpolarizing factor (EDHF)
KW - Epoxyeicosatrienoic acids (EETs)
KW - Kidney
KW - Microcirculation
KW - Renal blood flow
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U2 - 10.1038/sj.bjp.0702662
DO - 10.1038/sj.bjp.0702662
M3 - Article
C2 - 10455289
AN - SCOPUS:0032784521
SN - 0007-1188
VL - 127
SP - 1399
EP - 1405
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -