Salutary effects of nitrendipine, a new calcium entry blocker, in hemorrhagic shock

Carl E. Hock, Jing Yi Su, Allan M. Lefer

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Intracellular accumulation of calcium is thought to play an integral role in the progression of ischemic injury and cell death. We infused the calcium entry blocker, nitrendipine (1.5 μg/kg per min), into cats in order to investigate the importance of extracellular Ca2+ influx during hemorrhagic shock. Nitrendipine proved to be a potent hypotensive agent in sham shock cats when infused over a 4 h period (156 ± 9 to 90 ± 5 mm Hg) (P < 0.01). However, in hemorrhaged animals, nitrendipine treatment maintained the post-reinfusion MABP at a significantly higher (P < 0.01) value than untreated controls (79 ± 5 vs. 51 ± 4 mm Hg, respectively). Superior mesenteric artery flow (SMAF) for hemorrhaged animals treated with nitrendipine was significantly higher (9.8 ± 1.4 ml/min per kg) (P < 0.01) than that for untreated cats (4.2 ± 0.4 ml/min per kg), at 2 h post reinfusion. There was no significantly increase in SMAF during oligemia in the nitrendipine-treated animals. Nitrendipine was also found to significantly retard the appearance of cathepsin D in the plasma of hemorrhaged cats as well as reduce plasma proteolysis to values not significantly different from sham shock animals. Furthermore, myocardial depressant factor (MDF) activity in the plasma of nitrendipine-treated shock cats was not significantly different from sham shock animals, while the plasma MDF activity for shock cats receiving vehicle increased 3-fold (P < 0.001). The beneficial effects for nitrendipine in hemorrhagic shock are likely due to both its vasodilator function and its ability to reduce intracellular Ca2+ accumulation during ischemia, thereby reducing disruption of cell membrane systems.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalEuropean Journal of Pharmacology
Volume97
Issue number1-2
DOIs
StatePublished - Jan 13 1984
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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