Contractile responsiveness of aortic rings from control and endotoxin-shocked guinea pigs was examined in vitro. Aortae were removed 16 h following intraperitoneal administration of 4 mg/kg of Escherichia coli endotoxin or sterile saline. Although no shift in the dose-response curve or maximal contraction to norepinephrine (10(-9)-10(-4) M) was observed, there was an enhanced contractile response to KCl in shock rings. Calcium dose-response curves in both 60 mM and normal (5.4 mM) KCl were shifted upward in shock rings. This upward shift was abolished in normal KCl in the presence of the Ca2+ blocker D 600 (50 microM), suggesting enhanced Ca2+ influx via voltage-dependent Ca2+ channels in shock vascular smooth muscle. A deleterious effect of high cytoplasmic Ca2+ on vascular smooth muscle mitochondrial function may play a role in endotoxin shock.
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