Calcium channel blockers induce thymic apoptosis in vivo in rats

Arun Balakumaran, Gerald Campbell, Mary Treinen Moslen

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Abstract

We investigated the in vivo effect of structurally different calcium channel blockers (CCB) on rat thymus. Administration of verapamil (40 mg/kg ip), diltiazem (90 mg/kg ip), nifedipine (15 mg/kg ip), or nicardipine (10 mg/kg ip) induced apoptotic indices of 4.3, 4.0, 2.0, and 6.5, respectively, compared to 0.5 in the saline-treated control rats. Apoptosis was assessed by morphology and the apoptotic index was calculated using a computer-assisted image analyzer. Diltiazem had a rapid and substantial effect as evidenced by apoptosis at 1.5 hr and a 36% decrease in thymus weight by 24 hr. We were uncertain about the mechanisms by which CCB induced thymic apoptosis in vivo since in vitro studies have shown that increases in intracellular calcium cause apoptosis and that CCB prevent apoptosis. We sought insight into the mechanism by evaluating potential and known in vivo effects of these drugs. Neither verapamil nor diltiazem was found to elevate serum cortisol levels, a known trigger for apoptosis. Hypotension, a known response to CCB, does not appear to be causal factor since the potent hypotensive agent sodium nitroprusside (10 μg/kg, iv) did not cause a significant increase in thymic apoptosis. Calcium signaling may be important since the calmodulin antagonist chlorpromazine (60 mg/kg ip) was found to induce a 15-fold increase in apoptosis. Our observations suggest that calcium signaling is necessary for the survival of the T lymphocytes in the thymus.

Original languageEnglish (US)
Pages (from-to)122-127
Number of pages6
JournalToxicology and Applied Pharmacology
Volume139
Issue number1
DOIs
StatePublished - Jul 1996

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Calcium Channel Blockers
Rats
Apoptosis
Thymus
Diltiazem
Thymus Gland
Calcium Signaling
Verapamil
Calcium
Rat control
Nicardipine
T-cells
Chlorpromazine
Nitroprusside
Calmodulin
Nifedipine
Hypotension
Hydrocortisone
T-Lymphocytes
Weights and Measures

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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Calcium channel blockers induce thymic apoptosis in vivo in rats. / Balakumaran, Arun; Campbell, Gerald; Moslen, Mary Treinen.

In: Toxicology and Applied Pharmacology, Vol. 139, No. 1, 07.1996, p. 122-127.

Research output: Contribution to journalArticle

Balakumaran, Arun ; Campbell, Gerald ; Moslen, Mary Treinen. / Calcium channel blockers induce thymic apoptosis in vivo in rats. In: Toxicology and Applied Pharmacology. 1996 ; Vol. 139, No. 1. pp. 122-127.
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