Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. Am J Physiol 1994 May;266(5 Pt 2):H1879-85
Date
05/01/1994Pubmed ID
8203587DOI
10.1152/ajpheart.1994.266.5.H1879Scopus ID
2-s2.0-0028335404 (requires institutional sign-in at Scopus site) 86 CitationsAbstract
The present study evaluated the effects of cytochrome P-450 inhibitors on the response of the renal microvasculature to changes in renal perfusion pressure and on autoregulation of glomerular capillary pressure using the rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free perfusate containing 5% albumin. The basal diameters of the proximal and distal afferent arterioles averaged 28 +/- 1 (n = 32) and 18 +/- 1 micron (n = 23), respectively, at a control perfusion pressure of 80 mmHg. The diameters of these vessels decreased by 8% when perfusion pressure was elevated from 80 to 160 mmHg. After addition of cytochrome P-450 inhibitors (either 17-octadecynoic acid, 20 microM; 7-ethoxyresorufin, 10 microM; or miconazole, 20 microM) to the perfusate, the diameters of the proximal and distal afferent arterioles increased by 6% in response to the same elevation in perfusion pressure. Control glomerular capillary pressure averaged 43 +/- 1 mmHg (n = 32) at a renal perfusion pressure of 80 mmHg and increased by only 9 +/- 1 mmHg when perfusion pressure was elevated to 160 mmHg. Autoregulation of glomerular capillary pressure was impaired after addition of the cytochrome P-450 inhibitors, and it increased by 18 +/- 2 mmHg when perfusion pressure was varied over the same range. These results indicate that cytochrome P-450 inhibitors attenuate the vasoconstrictor response of afferent arterioles to elevations in renal perfusion pressure and impair autoregulation of glomerular capillary pressure, suggesting a possible role for cytochrome P-450 metabolites of arachidonic acid in these responses.
Author List
Imig JD, Zou AP, Ortiz de Montellano PR, Sui Z, Roman RJMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Arachidonic Acid
Arterioles
Cytochrome P-450 Enzyme Inhibitors
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Kidney
Kidney Cortex
Miconazole
Microsomes
Muscle, Smooth, Vascular
Oxazines
Perfusion
Rats
Rats, Sprague-Dawley
Renal Circulation
