Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness. Br J Pharmacol 1999 Jul;127(6):1399-405
Date
08/24/1999Pubmed ID
10455289Pubmed Central ID
PMC1760652DOI
10.1038/sj.bjp.0702662Scopus ID
2-s2.0-0032784521 (requires institutional sign-in at Scopus site) 82 CitationsAbstract
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. Afferent arteriolar diameter was measured as renal perfusion pressure was increased from 80-160 mmHg. Afferent arteriolar diameter averaged 19+/-2 microm at a renal perfusion pressure of 80 mmHg and decreased by 15+/-2% when pressure was increased to 160 mmHg. 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 microM PPOH, afferent arteriolar diameter decreased by 29+/-4% when pressure was increased from 80-160 mmHg. Likewise, the sulphonimide derivative of PPOH, N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (MS-PPOH, 50 microM), enhanced the afferent arteriolar response to increasing renal perfusion pressure. 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 microM DDMS, afferent arteriolar diameter decreased by 4+/-2% when pressure was increased from 80-160 mmHg. 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.
Author List
Imig JD, Falck JR, Inscho EWMESH terms used to index this publication - Major topics in bold
AmidesAnimals
Arterioles
Caproates
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Enzyme Inhibitors
Homeostasis
Kidney
Male
Mixed Function Oxygenases
Oxygenases
Perfusion
Pressure
Rats
Rats, Sprague-Dawley
Renal Artery
Signal Transduction
Sulfones
