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Dose-dependent autonomic dysfunction in chronic L-NAME-hypertensive diabetic rats
Adriana Werner Balbinott1, Maria Claudia Irigoyen, Maria do Socorro Brasileiro-Santos
1Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, Av. Princesa Isabel 370, Santana 90.620-001 Porto Alegre, RS, Brazil.
Journal of Cardiovascular Pharmacology
|October 13, 2005
Summary
High doses of L-NAME impaired autonomic function in rats, especially when combined with diabetes and hypertension. The study found autonomic dysfunction is linked to L-NAME dosage and disease state, not just arterial pressure.
Area of Science:
- Physiology
- Pharmacology
- Cardiovascular Research
Background:
- Diabetes mellitus is associated with autonomic dysfunction, affecting cardiovascular regulation.
- Nitric oxide synthase inhibition, using L-NAME, can impact arterial pressure and baroreflex sensitivity.
Purpose of the Study:
- To investigate the effects of varying L-NAME doses on arterial pressure, baroreflex control, and heart rate/arterial pressure variability.
- To assess these effects in both control and streptozotocin-induced diabetic rats.
Main Methods:
- Fifty-two Wistar rats were divided into diabetic (STZ-injected) and control groups.
- Animals received varying oral doses of L-NAME (10 or 30 mg/kg) or water for 14 days.
- Arterial pressure, heart rate, and their beat-to-beat variability were measured in conscious rats.
Main Results:
- L-NAME administration increased mean arterial pressure in both control and diabetic rats.
- Reflex tachycardia was blunted in a dose-dependent manner with L-NAME treatment.
- Heart rate and arterial pressure variability were reduced, with more pronounced dysfunction in diabetic rats receiving higher L-NAME doses.
Conclusions:
- Autonomic dysfunction induced by L-NAME is primarily related to the dose administered and the presence of diabetes and hypertension.
- The observed autonomic dysfunction is not solely dependent on elevated arterial pressure values.
- L-NAME dosage and the combination of diabetes with hypertension are key factors in autonomic dysfunction.