ATP utilization (δP) during an isometric contraction has been studied in terms of both measurements of oxygen consumption and lactate production as well as of the tissue nucleotide and metabolite levels. The contribution of breakdown of preformed ATP and phosphocreatine (PCr) pools to δP during contraction is minor compared to that made by metabolic synthesis of ATP. For tonic vascular smooth muscle (VSM), in fact, no change in ATP or PCr from resting levels can be measured. In contrast to amphibian skeletal muscle, a P:O of 3 can be demonstrated in VSM. In both tonic and phasic VSM, δP is biphasic with contraction duration, attaining a maximal value before that of isometric force and declining to a steady-state value approximately 60% of the maximal suprabasal rate during the maintenance of constant isometric force. The steady-state rate of ATP utilization per unit force maintained increases with extracellular Ca2+. Both the pre-steady-state temporal dependence and the steady-state dependence on Ca2+ are consistent with the hypothesis that myosin phosphorylation modulates the cross-bridge cycle rates. VSM metabolism, when viewed in terms of ATP synthesis, is primarily oxidative. However, even under fully oxygenated conditions, lactate is the major end product of glucose catabolism. Recent work has shown that aerobic lactate production is specifically coupled to Na-K transport in many, but not all, vascular tissues. Oxidative metabolism, on the other hand, is strongly related to active isometric force. The biochemical basis of this functional compartmentation was investigated at the level of substrate specificity. In porcine carotid artery, glucose is the sole substrate for aerobic lactate production, even under conditions where substantial glycogen breakdown can be demonstrated. The compartmentation of glycogenolysis and glycolysis appears to mirror the functional compartmentation. Moreover, in this tissue, transmembrane glucose transport is rate-limiting to its catabolism. Thus, the increased lactate production observed on stimulation of Na-K transport must be coordinated with an increase in glucose transport. The mechanism underlying this coordination is unknown, but it may be of particular significance in hypertension and aging, cases in which vascular glycolysis and ion transport are increased.
- Ion transport
- Oxidative metabolism
- Vascular smooth muscle
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine