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In helically-cut strips of cerebral arteries isolated from dogs and monkeys, the addition of 1 mM iodoacetic acid (IAA) produced contractions during an early period (5 to 10 min) and also a prolonged exposure (50 to 70 min). The early contraction was abolished by exposure to Ca++-free media containing EGTA, and significantly attenuated by treatment with procaine or dantrolene. Verapamil, lidocaine, ATP and pyruvate did not inhibit the contraction. On the other hand, the late contraction was not prevented by exposure to Ca++-free, EGTA-containing media and by treatment with procaine, dantrolene, lidocaine, ATP or pyruvate. Nitroglycerin and papaverine did not relax the IAA-contracted arteries. In dog and monkey mesenteric arteries and dog coronary, renal and femoral arteries, IAA elicited contractions after a prolonged exposure, which were not inhibited by soaking the preparations in Ca++-free, EGTA-containing media. Passive tensions developed by rapid stretch in Ca++-free media did not differ in IAA-treated and control arteries. During an early period of IAA actions, Ca++ appears to be released from intracellularly stored sites in the amount sufficient to produce significant contractions in cerebral, but not in peripheral arteries. It is concluded that the involvement of Ca++ in the late contraction induced by IAA is if any minimal, and such a contraction may be associated with functional alterations induced by the metabolic inhibitor in arterial tissues other than smooth muscle.

The ultrastructure, volume, vital-dye uptake, ATP levels and amounts of intracelular water have been studied in Ehrlich ascites cells treated with two classes of inhibitors. Cell membrane injury with 10(-3) M parachloromercuribenzene sulfonate (PCMBS) resulted in a rapid increase in mean cell volume to 3 times the mean zero time value. Inhibition of respiration plus glycolysis with 10(-4) M iodoacetate (IAA) plus 10(-4) M antimycin resulted first in a slight decrease in volume and then later a slow increase. When glucose was present in the medium, this slow increase was very slight. Intracellular water determination followed closely the volume changes. Cell populations with decreased mean volumes showed dilatations of the ER and swelling of mitochondria, indicating that expansion of some intracellular compartments can occur at the expense of others. Vital-dye uptake in metabolic injury correlated to some extent with the presence of substrate, indicating that an effect of glucose on membrane permeability might be independent of its effects on ATP levels. Mitochondrial contractions appeared with PCMBS as early as 5 minutes, with or without glucose present. With glucose present, treatment with IAA and antimycin also resulted in similar contractions as well as ring-form contractions even at 5 minutes. Without glucose, IAA plus antimycin mainly produced the usual mitochondrial contractions and these developed much later in the course of the incubation, shortly before high-amplitude swelling. The relationship of these mitochondrial conformational changes to ADP/ATP ratios and ADP levels is discussed.