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Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats. Hypertension 1997 Jan;29(1 Pt 2):315-9

Date

01/01/1997

Pubmed ID

9039121

DOI

10.1161/01.hyp.29.1.315

Scopus ID

2-s2.0-0031025761 (requires institutional sign-in at Scopus site)   76 Citations

Abstract

Recent studies have indicated that a deficiency in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may contribute to the abnormalities in the renal handling of sodium and the development of hypertension in Dahl salt-sensitive rats. To determine whether a reduction in 20-HETE production in the outer medulla is sufficient to induce hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450 enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min) reduced the formation of 20-HETE in the outer medulla of the infused kidney by 70% compared with values seen in the right kidney collected when the rat was uninephrectomized, but it had no effect on the production of 20-HETE in the renal cortex. After 5 days, mean arterial pressure rose from 115 +/- 2 to 142 +/- 2 mm Hg (n = 6) in the rats infused with 17-ODYA, while mean arterial pressure was not significantly altered in the rats infused with vehicle alone (116 +/- 1 versus 117 +/- 2 mm Hg, n = 6). These results suggest that inhibition of the renal metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney is sufficient to induce the development of hypertension in Lewis rats fed a high salt diet and support the view that P450 metabolites of arachidonic acid play an important role in the regulation of renal function and the long-term control of arterial pressure.

Author List

Stec DE, Mattson DL, Roman RJ

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Hydroxyeicosatetraenoic Acids
Hypertension
Kidney Medulla
Microsomes
Oleic Acids
Rats
Rats, Inbred Lew
Steroid Hydroxylases