Calcium entry blockade prevents leakage of macromolecules induced by ischemia-reperfusion in skeletal muscle

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Calcium kinetics and its intracellular mobilization are important in all biological processes. We used verapamil to examine the effect of calcium entry blockade on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-conjugated dextran (FITC-dextran 150) was measured as an index of microvascular transport. After determination of baseline data (clearance of FITC-dextran 150, 3.0 ± 0.5 μl/5 min/g), the muscle was made ischemic for 2 hours by clamping its vascular pedicle and subsequently was reperfused for 2 hours. Ischemia-reperfusion produced a marked increase in FITC-dextran clearance. After a peak of 12 ± 2-fold increase observed in the first 15 minutes into reperfusion, FITC-dextran 150 clearance decreased in magnitude and stabilized at about sixfold above baseline. Verapamil did not change the baseline clearance values. Importantly, verapamil inhibited the ischemia-induced increase in clearance and maintained the values at or near the baseline levels. We simultaneously determined the rate of release of 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)) and thromboxane B2 (TXB2) into the suffusate. Verapamil decreased the baseline values of 6-keto-PGF(1α) and increased those of TXB2. Verapamil inhibited the ischemia-reperfusion-induced increase in 6-keto-PGF(1α) but did not alter the effect of ischemia-reperfusion on TXB2. Our main results demonstrate the effectiveness of verapamil in preventing microvascular alterations leading to increased leakage of macromolecules.

Original languageEnglish (US)
Pages (from-to)1636-1642
Number of pages7
JournalCirculation Research
Issue number6
StatePublished - 1990

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology


  • calcium entry blockade
  • ischemia-reperfusion injury
  • microvascular permeability
  • prostacyclin
  • skeletal muscle
  • thromboxane A
  • verapamil


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