The Role of Renal Medullary Bilirubin and Biliverdin Reductase in Angiotensin II-Dependent Hypertension.

Autor:	Arthur G; Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216 USA., Wasson AR; Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216 USA., Straughan RE; Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216 USA., Drummond HA; Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216 USA., Stec DE; Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216 USA.
Jazyk:	angličtina
Zdroj:	American journal of hypertension [Am J Hypertens] 2024 Dec 04. Date of Electronic Publication: 2024 Dec 04.
DOI:	10.1093/ajh/hpae150
Abstrakt:	Background: Increased circulating bilirubin attenuates angiotensin (Ang) II-induced hypertension and improves renal hemodynamics. However, the intrarenal mechanisms that mediate these effects are not known. The goal of the present study was to test the hypothesis that bilirubin generation in the renal medulla plays a protective role against Ang II-induced hypertension. Methods: Twenty-week-old male C57Bl/6J mice were implanted with intrarenal medullary interstitial (IRMI) catheters following unilateral nephrectomy. After this time, biliverdin IXα was specifically infused into the kidney (3.6 mg/day) for 3 days before implantation with an osmotic minipump delivering Ang II (1000 ng/kg/min). BP was recorded for 3 days, 1 week after minipump infusion, in conscious mice. To further explore the antihypertensive role of renal medullary bilirubin generation, mice with specific deletion of biliverdin reductase-A (Blvra) in the thick ascending loop of Henle (TALH) were generated. At 20 weeks, BlvraTALHKO and control mice (Blvrafl/fl) were infused with Ang II for 2 weeks. Results: IRMI infusion of biliverdin significantly decreased blood pressure compared to mice infused with vehicle (118 ± 4 vs. 158 ± 2 mmHg, p<0.05). Angiotensin-II infusion resulted in significantly higher blood pressure measured in conscious mice 7 days after implantation in BlvraTALHKO as compared to Blvrafl/fl mice (152 ± 2 vs. 140 ± 3 mmHg, p<0.05). Conclusions: Together, these findings show that medullary bilirubin and biliverdin reductase can improve hypertension and that mechanisms that increase bilirubin and biliverdin reductase in the renal medulla could be an effective approach to treat hypertension. (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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