Exercise hemodynamic and neurohormone responses as sensitive biomarkers for diltiazem in rats.
OBJECTIVE
To investigate the potential of exercise hemodyanamic and neurohormone variables as sensitive biomarkers for pre-clinical evaluation of diltiazem (DTZ).


METHODS
Sprague Dawley (SD) rats were randomly divided into 3 groups (n = 6 - 8 each), and each group received DTZ 10 mg/kg twice daily for 5 doses or saline followed by a treadmill exercise protocol for 7 min with speed set at 7 m/min at 3 % grade. The 3rd group received saline but no exercise.


RESULTS
Exercise increased SBP from 108 +/- 2 to 131 +/- 3 mmHg, and HR from 437 +/- 6 to 503 +/- 6 bpm, and plasma epinephrine concentrations from 2.0 +/- 0.6 to 5.8 +/- 1.7 ng/mL in control rats (p < 0.05 for all variables), but had no significant effect on DBP (81 +/- 5 vs 87 +/- 6 mmHg) and plasma norepinephrine concentrations (1.5 +/- 0.2 vs 3.9 +/- 0.4 ng/mL). The hemodynamic responses to exercise were significantly attenuated by DTZ (p < 0.05), but the effect on neurohormone response was minimal (p > 0.05).


CONCLUSIONS
Exercise hemodynamic and neurohormone responses are sensitive biomarkers which could be used for safety and efficacy evaluation of DTZ and perhaps also other calcium antagonists in pre-clinical animal models.
Yeung
Pollen K F
PK
Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of Medicine, Faculties of Health Professions and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. Pollen.Yeung@Dal.Ca
Feng
Joe D
JD
Fice
Debbra
D
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D004110:Diltiazem