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Effects of chronic norepinephrine administration on cardiac function in rats
S K Laycock1, J McMurray, K A Kane
1Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Journal of Cardiovascular Pharmacology
|October 1, 1995
Summary
Chronic norepinephrine (NE) exposure in rats caused cardiac changes, including hypertrophy and reduced contractile responses. Free radical production was linked only to high NE doses causing significant mortality.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Chronic norepinephrine (NE) exposure can alter cardiac function.
- The role of free radicals in NE-induced cardiac changes requires further investigation.
Purpose of the Study:
- To evaluate the impact of chronic norepinephrine administration on rat heart contractile responses.
- To determine if free radical production is involved in these cardiac alterations.
Main Methods:
- Male rats received chronic subcutaneous administration of norepinephrine (0.15-0.35 mg/kg/h) or saline via osmotic minipumps for 10-28 days.
- Hemodynamic measurements and dose-response curves to NE and calcium chloride were performed.
- Plasma thiobarbituric acid-reactive substances (TBARS) were measured to assess free radical activity.
Main Results:
- Chronic NE induced left ventricular hypertrophy across all doses.
- Lower NE doses increased basal left ventricular pressure generation and systolic blood pressure.
- Reduced responses to acute NE administration were observed, while calcium chloride responses were unaffected.
- Increased plasma free radicals and high mortality were associated only with the highest NE dose.
Conclusions:
- Chronic NE administration leads to beta-adrenoceptor downregulation.
- Free radical production is linked to high-dose NE exposure and mortality, suggesting a role in severe cardiotoxicity.