Alexandra Sporková1, Rami N Reddy2, John R Falck2, John D Imig3, Libor Kopkan4, Janusz Sadowski5, Luděk Červenka6. 1. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: alhc@medicon.cz. 2. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas. 3. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin. 4. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5. Department of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Science, Warsaw, Poland. 6. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Abstract
BACKGROUND: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. MATERIALS AND METHODS: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-ether-EET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. RESULTS: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4% versus 80.4 ± 6%, and for native EETs they were 41.7 ± 6.6% versus 62.8 ± 4.4% (P ≤ 0.05 for each difference). CONCLUSIONS: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension.
BACKGROUND: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensiverats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. MATERIALS AND METHODS: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-ether-EET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. RESULTS: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4% versus 80.4 ± 6%, and for native EETs they were 41.7 ± 6.6% versus 62.8 ± 4.4% (P ≤ 0.05 for each difference). CONCLUSIONS: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensiverats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensiverats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of humanrenovascular hypertension.
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: Agnieszka Walkowska; Luděk Červenka; John D Imig; John R Falck; Janusz Sadowski; Elżbieta Kompanowska-Jezierska Journal: Front Physiol Date: 2021-01-28 Impact factor: 4.566