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Related Experiment Videos

Cyclosporine-induced hypotension.

G W Parkhurst1, B H Moon, R L Xia

  • 1Department of Pharmacology, Rush Medical College, Chicago, Illinois 60612.

Transplantation
|November 1, 1989
PubMed
Summary

Cyclosporine (CsA) infusion causes dose-dependent hypotension in rabbits by reducing sympathetic activity. This immunosuppressant drug

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Area of Science:

  • Pharmacology
  • Cardiovascular Physiology
  • Immunosuppression

Background:

  • Cyclosporine (CsA) is a widely used immunosuppressant.
  • Its cardiovascular effects, particularly hypotension, require further elucidation.
  • Understanding CsA's impact on blood pressure is crucial for patient management.

Purpose of the Study:

  • To investigate the cardiovascular effects of intravenous cyclosporine infusion in rabbits.
  • To determine the dose-dependent relationship between CsA and hypotension.
  • To elucidate the underlying mechanisms of CsA-induced hypotension.

Main Methods:

  • Intravenous infusion of cyclosporine (0.5–120 mg/kg/hr) in pentobarbital-anesthetized rabbits.
  • Monitoring of heart rate and blood pressure.
  • Assessment of cardiovascular reflexes (vagal stimulation, carotid occlusion) before and after CsA infusion.
  • Evaluation of CsA's interaction with cholinergic and adrenergic systems, and prostaglandin metabolism.

Main Results:

  • CsA induced significant, sustained, and dose-dependent hypotension.
  • At 60 mg/kg/hr, diastolic blood pressure dropped by 27 mmHg.
  • CsA attenuated cardiovascular reflex responses, including response to carotid occlusion.
  • No significant changes in response to vagal stimulation were observed.
  • The hypotensive effect was not altered by glycopyrrolate or aspirin.

Conclusions:

  • Cyclosporine-induced hypotension in rabbits is primarily mediated by a decrease in endogenous sympathetic adrenergic activity.
  • Cholinergic tone, ganglionic transmission, and vasodilatory prostaglandin metabolism are not the primary mechanisms.
  • This study provides insights into the cardiovascular safety profile of cyclosporine.

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