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  2. BAY k 8644, a calcium channel agonist, reverses hypotension in endotoxin-shocked rats

BAY k 8644, a calcium channel agonist, reverses hypotension in endotoxin-shocked rats

  • Eur J Pharmacol. 1986 Nov 4;130(3):169-75. doi: 10.1016/0014-2999(86)90265-7.
N Ives J W King B Chernow B L Roth
Abstract

The hypotension and depressed myocardial function frequently observed in endotoxin-induced shock are difficult to overcome pharmacologically. In this paper we demonstrate that the Calcium Channel agonist BAY k 8644 potently elevates blood pressure in endotoxin-shocked rats. A one time dose as low as 10 micrograms/kg of BAY k 8644 significantly elevated mean arterial pressure (MAP) in endotoxin-treated hypotensive rats while having minimal effects in normal rats. The maximum BAY k-induced percentage increase in MAP was greater in endotoxin-treated rats when compared with saline-treated control (153% vs. 120% increase respectively). BAY k 8644 also caused a dose-dependent decrease in heart rate of 37% in endotoxin-treated rats and 39% in control rats (NS vs. control). No differences in the regulatory properties of [3H]nitrendipine binding sites were discerned comparing control and endotoxin-treated rats. Thus, the enhanced activity of BAY k 8644 in hypotensive rats was not due to augmented affinity for the cardiac dihydropyridine binding site. These results demonstrate that the use of Calcium Channel agonists might represent a unique pharmacologic approach in pathologic states characterized by hypotension and diminished cardiac function.

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