Role of cytochrome P-450 in elevating renal vascular tone in spontaneously hypertensive rats. J Vasc Res 1993;30(1):53-60
Date
01/01/1993Pubmed ID
8435472DOI
10.1159/000158975Scopus ID
2-s2.0-0027471234 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
The contribution of cytochrome P-450 metabolites of arachidonic acid in elevating vascular tone in the kidneys of adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was examined using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. At 80 mm Hg, the basal internal diameters of arcuate and interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 341 +/- 15.81 +/- 5.24 +/- 0.5 and 19 +/- 0.3 micron, respectively. These diameters were 5-29% smaller (p < 0.05) than those measured in corresponding vessels in WKY rats. Addition of the P-450 inhibitors, ketoconazole (100 microM) or 17-octadecynoic acid (17-ODYA, 20 microM), to the perfusate and bath increased the diameters of the preglomerular vasculature of the SHR by 6-29%, but by only 3-13% in WKY rats and reduced significantly the differences in pressure-diameter relations between the two groups. The rate of formation of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical microsomes was similar in SHR and WKY rats. However, the production of epoxyeicosatrienoic acids (EETs) by cortical microsomes was 87% lower and dihydroxyeicosatrienoic acids (DHETs) 70% higher in the SHR than WKY rats. Ketoconazole (100 microM) reduced the formation of 20-HETE by 80%, and EETs and DHETs production by more than 98% in SHR and WKY rats. 17-ODYA (20 microM) reduced the formation of 20-HETE, EETs and DHETs by more than 98% in both groups. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to the elevated renal vascular tone in adult SHR. This may be due to an enhanced vascular responsiveness to vasoconstrictor P-450 metabolites in SHR or an elevated local production of vasoconstrictor eicosanoids in the renal vasculature of SHR rather than in renal cortical tissue.
Author List
Gebremedhin D, Ma YH, Imig JD, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
AnimalsCytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Eicosanoids
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
Ketoconazole
Kidney
Microcirculation
Muscle, Smooth, Vascular
Rats
Rats, Inbred SHR
Rats, Inbred WKY
