Source Paper
Source Paper
Journal of Clinical Investigation • 1996
We tested the hypothesis that angiotensin II-induced hypertension is associated with an increase in vascular.O2- production, and characterized the oxidase involved in this process. Infusion of angiotensin II (0.7 mg/kg per d) increased systolic blood pressure and doubled vascular.O2- production (assessed by lucigenin chemiluminescence), predominantly from the vascular media. NE infusion (2.75 mg/kg per d) produced a similar degree of hypertension, but did not increase vascular.O2- production. Studies using various enzyme inhibitors and vascular homogenates suggested that the predominant source of.O2- activated by angiotensin II infusion is an NADH/NADPH-dependent, membrane-bound oxidase. Angiotensin II-, but not NE-, induced hypertension was associated with impaired relaxations to acetylcholine, the calcium ionophore A23187, and nitroglycerin. These relaxations were variably corrected by treatment of vessels with liposome-encapsulated superoxide dismutase. When Losartan was administered concomitantly with angiotensin II, vascular.O2- production and relaxations were normalized, demonstrating a role for the angiotensin type-1 receptor in these processes. We conclude that forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle.O2- production via NADH/NADPH oxidase activation.
Objective: Test the hypothesis that angiotensin II-induced hypertension is associated with increased vascular superoxide production and characterize the oxidase involved in this process
This is a Angiotensin II Infusion protocol using rat as the model organism. The procedure involves 7 procedural steps, 2 equipment items, 9 materials. Extracted from a 1996 paper published in Journal of Clinical Investigation.
Model and subjects
rat • Not specified • unknown • Not specified • Not specified
Study window
Estimated timing pending
Core workflow
Angiotensin II infusion • Norepinephrine infusion control • Measure vascular superoxide production
Primary readouts
Key equipment and reagents
Verified items
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Infuse angiotensin II systemically into rats at a dose of 0.7 mg/kg per day to induce hypertension
Note: This treatment increases systolic blood pressure and doubles vascular superoxide production
“Infusion of angiotensin II (0.7 mg/kg per d) increased systolic blood pressure and doubled vascular.O2- production”
Infuse norepinephrine systemically into control rats at a dose of 2.75 mg/kg per day to produce similar degree of hypertension
Note: This control treatment produces hypertension but does not increase vascular superoxide production
“NE infusion (2.75 mg/kg per d) produced a similar degree of hypertension, but did not increase vascular.O2- production”
Assess vascular superoxide production using lucigenin chemiluminescence in vascular tissue samples
Note: Superoxide production is predominantly from the vascular media
“doubled vascular.O2- production (assessed by lucigenin chemiluminescence), predominantly from the vascular media”
Use various enzyme inhibitors and vascular homogenates to identify the source of superoxide production
Note: Studies identified NADH/NADPH-dependent, membrane-bound oxidase as the predominant source
“Studies using various enzyme inhibitors and vascular homogenates suggested that the predominant source of.O2- activated by angiotensin II infusion is an NADH/NADPH-dependent, membrane-bound oxidase”
Test vascular relaxation responses to acetylcholine, calcium ionophore A23187, and nitroglycerin
Note: Angiotensin II-induced hypertension impairs relaxations to these agents, while NE-induced hypertension does not
“Angiotensin II-, but not NE-, induced hypertension was associated with impaired relaxations to acetylcholine, the calcium ionophore A23187, and nitroglycerin”
Treat vessels with liposome-encapsulated superoxide dismutase to determine if it corrects impaired relaxations
Note: Treatment variably corrected the impaired relaxations
“These relaxations were variably corrected by treatment of vessels with liposome-encapsulated superoxide dismutase”
Administer Losartan (angiotensin type-1 receptor antagonist) concomitantly with angiotensin II infusion
Note: Losartan normalizes vascular superoxide production and relaxations, demonstrating a role for angiotensin type-1 receptor
“When Losartan was administered concomitantly with angiotensin II, vascular.O2- production and relaxations were normalized, demonstrating a role for the angiotensin type-1 receptor”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Test the hypothesis that angiotensin II-induced hypertension is associated with increased vascular superoxide production and characterize the oxidase involved in this process
Objective
Test the hypothesis that angiotensin II-induced hypertension is associated with increased vascular superoxide production and characterize the oxidase involved in this process
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperNone specified
Angiotensin II infusion (Not specified)
Norepinephrine infusion control (Not specified)
Measure vascular superoxide production (Not specified)
Characterize oxidase source (Not specified)
Systolic blood pressure
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Vascular superoxide production (measured by lucigenin chemiluminescence)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Location of superoxide production (vascular media)
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Vascular relaxation responses to acetylcholine
From paperNot specified in the provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Systolic blood pressure
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Vascular superoxide production (measured by lucigenin chemiluminescence)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Location of superoxide production (vascular media)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Vascular relaxation responses to acetylcholine
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified in the provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Systolic blood pressure; Vascular superoxide production (measured by lucigenin chemiluminescence); Location of superoxide production (vascular media); Vascular relaxation responses to acetylcholine.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Systolic blood pressure, Vascular superoxide production (measured by lucigenin chemiluminescence), Location of superoxide production (vascular media), Vascular relaxation responses to acetylcholine.
Source links and direct wording from the methods section for validation and deeper review.
Citation
S Rajagopalan et al. (1996). Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.. Journal of Clinical Investigation
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Evidence Quotes
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Protocol Items
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Evidence
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