Substrates and vascular smooth muscle contraction

Abstract

Rabbit aorta suspended in a substrate-free medium develops undiminishing tension responses to repeated stimulation with physiological concentrations of epinephrine (1-10 jug/1), indicating a considerable endogenous energy reserve in this vascular smooth muscle. After repeated short-term or single sustained stimulation with higher concentrations of epinephrine (1-10 mg/1), contractility is diminished, suggesting that the energy reserve can be at least partially depleted which is confirmed by the reaction of the response to normal when substrates are added back to the external medium. This recovery phenomenon implies the presence of metabolic pathways which can use the added substrate to produce energy for contraction. Glucose and mannose are readily utilized, suggesting the presence of the Embden-Meyerhof pathway. Although the Krebs intermediates themselves are not used directly, and therefore probably do not gain entrance into the mitochondria, Krebs cycle is evident since lactate and pyruvate are among the most effective substrates tested. This pathway, as well as a beta oxidative pathway for fatty acid degradation, must also account for the recovery produced by butyrate, oleate, acetoacetate and beta hydroxybutyrate. Some substrates (Krebs intermediates and certain amino acids) are not utilized, which suggests that their movement into the cells is minimal, or that the appropriate activating enzymes are not present in vascular tissue.