Cytochrome P450 1B1 and 12/15 Lipoxygenase Interaction in Paraventricular Nucleus in Angiotensin II-induced Hypertension in Females
type: CreativeWork
description: Background: Angiotensin (Ang) II releases arachidonic acid (AA) from tissue phospholipids that is metabolized by 12/15-lipoxygenase (ALOX15) generating 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) which have been implicated in cardiovascular and renal diseases. This study was conducted to investigate a) the contribution of ALOX15 to Ang II-induced hypertension and associated pathogenesis in female mice, and b) the interaction between the cytochrome P450 (CYP)1B1-generated metabolite of 17β-estradiol (E2) (2-methoxyestradiol, 2-ME) and ALOX15 in the paraventricular nucleus (PVN) as a mechanism that protects against Ang II-induced hypertension and its associated pathogenesis in female mice. Methods: Experiments were conducted in intact and ovariectomized (OVX) wild type (WT), alox15 knockout (ALOX15KO) and CYP1B1KO female mice. Ang II (700 ng/kg/min) was infused subcutaneously by osmotic pumps for 2 weeks evaluation of hypertension and associated pathogenesis. Blood pressure (BP) was measured by tail-cuff and confirmed by radiotelemetry. Adenoviral probes including adenovirus (Ad)-green fluorescence (GFP)-ALOX15-short hairpin (sh)RNA, Ad-GFP-ALOX15-DNA, and their respective controls Ad-scrambled shRNA and Ad-GFP-DNA, 12(S)-HETE and 2-ME were injected in the brain using stereotaxic technique, either selectively in PVN or intracerebroventricularly via ICV cannula implanted in the right lateral ventricle to study their roles on Ang II-induced hypertension. Histological, immunohistochemical, and fluorescence microscopy and biochemical techniques were employed to determine the pathophysiological changes in tissues. ELISA was used for the analysis of sex steroids and eicosanoids. Results: Our results demonstrate that the effects of Ang II to increase BP, impair autonomic function and increase renal reactive oxygen species (ROS) production and plasma 12(S)-HETE but not 15(S)-HETE level without altering renal function in intact WT mice were exacerbated in OVX-WT mice.…
abstract: Background: Angiotensin (Ang) II releases arachidonic acid (AA) from tissue phospholipids that is metabolized by 12/15-lipoxygenase (ALOX15) generating 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) which have been implicated in cardiovascular and renal diseases. This study was conducted to investigate a) the contribution of ALOX15 to Ang II-induced hypertension and associated pathogenesis in female mice, and b) the interaction between the cytochrome P450 (CYP)1B1-generated metabolite of 17β-estradiol (E2) (2-methoxyestradiol, 2-ME) and ALOX15 in the paraventricular nucleus (PVN) as a mechanism that protects against Ang II-induced hypertension and its associated pathogenesis in female mice. Methods: Experiments were conducted in intact and ovariectomized (OVX) wild type (WT), alox15 knockout (ALOX15KO) and CYP1B1KO female mice. Ang II (700 ng/kg/min) was infused subcutaneously by osmotic pumps for 2 weeks evaluation of hypertension and associated pathogenesis. Blood pressure (BP) was measured by tail-cuff and confirmed by radiotelemetry. Adenoviral probes including adenovirus (Ad)-green fluorescence (GFP)-ALOX15-short hairpin (sh)RNA, Ad-GFP-ALOX15-DNA, and their respective controls Ad-scrambled shRNA and Ad-GFP-DNA, 12(S)-HETE and 2-ME were injected in the brain using stereotaxic technique, either selectively in PVN or intracerebroventricularly via ICV cannula implanted in the right lateral ventricle to study their roles on Ang II-induced hypertension. Histological, immunohistochemical, and fluorescence microscopy and biochemical techniques were employed to determine the pathophysiological changes in tissues. ELISA was used for the analysis of sex steroids and eicosanoids. Results: Our results demonstrate that the effects of Ang II to increase BP, impair autonomic function and increase renal reactive oxygen species (ROS) production and plasma 12(S)-HETE but not 15(S)-HETE level without altering renal function in intact WT mice were exacerbated in OVX-WT mice.…
author: Dutta, Shubha Ranjan
keywords: 12/15-Lipoxygenase, 17Beta-Estradiol, Angiotensin II, Hypertension, Kidney pathogenesis, Ovariectomy, Cardiovascular Diseases, Diseases, Medical Pharmacology, Medicine and Health Sciences
date published: 2023-05-01T07:00:00Z
date modified: 2026-07-24T05:00:53Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center