Vascular effects of the Krebs intermediate metabolites

The vascular effects of seven intermediary products of oxidative metabolism (acetate, citrate, fumarate, malate, α-ketoglutarate, oxalacetate, and succinate) were studied on the constantly perfused kidney or forelimb in 32 dogs. Significant vasodilation was obtained at submaximal dosages, usually 2.47 µmole/min, in both vascular beds for all agents without changing systemic pressure. At maximal infusion rates renal resistance decreased approximately 20%. Saline had no effect. When segmental resistances were calculated for the forelimb by measuring pressures in large and small arteries and veins, active dilation was localized to small vessel segment (25% fall). Arterial and venous segment resistances were unchanged. It is concluded that the Krebs intermediates should be included among those agents termed "vasodilating metabolites," and that these compounds could be exceedingly important in the local regulation of blood flow.