OBJECTIVE: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. METHODS: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, omega-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. RESULTS: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. CONCLUSION: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.
OBJECTIVE: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensiverats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. METHODS: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, omega-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. RESULTS: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. CONCLUSION: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.
Authors: Z Yu; F Xu; L M Huse; C Morisseau; A J Draper; J W Newman; C Parker; L Graham; M M Engler; B D Hammock; D C Zeldin; D L Kroetz Journal: Circ Res Date: 2000-11-24 Impact factor: 17.367
Authors: John D Imig; Xueying Zhao; Constantine Z Zaharis; Jeffrey J Olearczyk; David M Pollock; John W Newman; In-Hae Kim; Takaho Watanabe; Bruce D Hammock Journal: Hypertension Date: 2005-09-12 Impact factor: 10.190
Authors: M M Muthalif; N A Karzoun; L Gaber; Z Khandekar; I F Benter; A E Saeed; J H Parmentier; A Estes; K U Malik Journal: Hypertension Date: 2000-10 Impact factor: 10.190
Authors: Ludek Cervenka; Ivana Vanecková; Zuzana Husková; Zdenka Vanourková; Michaela Erbanová; Monika Thumová; Petra Skaroupková; Martin Opocenský; Jan Malý; Vera Certíková Chábová; Vladimír Tesar; Marcela Bürgelová; Ondrej Viklický; Vladimír Teplan; Michal Zelízko; Herbert J Kramer; L Gabriel Navar Journal: J Hypertens Date: 2008-07 Impact factor: 4.844
Authors: Jan Neckář; Libor Kopkan; Zuzana Husková; František Kolář; František Papoušek; Herbert J Kramer; Sung Hee Hwang; Bruce D Hammock; John D Imig; Jiří Malý; Ivan Netuka; Bohuslav Ošťádal; Luděk Červenka Journal: Clin Sci (Lond) Date: 2012-06 Impact factor: 6.124
Authors: Alexandra Sporková; Rami N Reddy; John R Falck; John D Imig; Libor Kopkan; Janusz Sadowski; Luděk Červenka Journal: Am J Med Sci Date: 2016-02-23 Impact factor: 2.378