The proposed research involves an investigation of the relationship of intermediary metabolism to the energy requiring processes of contraction and maintenance of the ionic environment in the isolated rat anococcygeus smooth muscle. Ths muscle, like arterial vascular smooth muscle, is innervated by adrenergic nerves and maintains sustained tonic contractions. A suitable chemically-denervated preparation will be developed in order to eliminate effects of endogenous catecholamines on the contractile and metabolic response measured. The optimal conditions for maximal isometri force production will be defined by determining the active and passive length-tension relationship and by examining the effects of different chemical stimuli on the strength and duration of the force response Measurements of steady state rates of lactate production and oxygen consumption will be used to estimate the ATP utilized by the muscle. The relationship of energy utilization to force production will be determined under conditions where the developed force is varied by altering either the muscle length or the concentration of the chemical stimulus in order to calculate the energy utilized fdor tension-dependent and tension-indenpendent processes. The influence on these parameters on altering the activity of the Na+ K+ pump will be investigated to derermine 1) whether the ATP derived from oxidative phosphorylation is correlated with force production, and 2) whether the ATP for the Na+ K+ATPase is specifically generated by aerobic glycolysis. The following experiments on glycogen and exogenous glucose metabolism using radioisotope-labeling techniques will test the hypothesis that functionally separated glycolytic pathways exist in these muscles: 1) effects of non-carbohydrate substrates on force, lactate production, and oxygen consumption; 2) effects of inhibition of the Na+K+pump on glucose transport; and 3) the relative ontribution of glycogen and exogenous glucose to lactate and CO2 production under conditions in which both the Na+ K+ pump and force production are inhibited. An understanding of both the energy requirements and the metabolic pathways coupled to specific cellular processes in normal smooth muscle, under mechanically defined conditions would provide a basis for the design and interpretation of future energetics studies in hypertensive and diabetic animal models.
| Davidheiser, S (1986) Metabolic differences between norepinephrine- and K+-stimulated anococcygeus muscle. Am J Physiol 251:C72-7 |
