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The relation between pO2 and beta adrenergic responsiveness was studied in isolated bovine and porcine coronary artery rings. Isoproterenol elicited a concentration-dependent relaxation of bovine and porcine coronary artery rings precontracted with KCI (2 X 10(-2) M) or histamine (10(-6) M); beta adrenergic responsiveness was significantly lower in K+-depolarized coronary arteries. A decrease of bath pO2 from 95 to 40% significantly reduced beta adrenergic responsiveness in both coronary preparations precontracted with either KCI or histamine. Similarly, exogenous arachidonic acid (3 X 10(-6) to 3 X 10(-5) M) depressed isoproterenol-induced relaxations in both tissues. Indomethacin (5 X 10(-6) M) augmented beta adrenergic responsiveness in the presence of 95% O2 and prevented the inhibitory effects of the decrease in bath pO2 and arachidonic acid in both preparations. The experimental data suggest that the demonstrated O2-sensitivity of beta adrenergic responsiveness is mediated by vascular prostaglandin synthesis in isolated large coronary arteries.

The metabolism of vascular smooth muscle is characterized by an unusual component of aerobic glycolysis. Lactate production, even under fully oxygenated conditions, is of similar magnitude to the rate of oxygen consumption when compared on a molar basis. Although the underlying mechanisms are unknown, the ratio of glycolytic to oxidative metabolism has been suggested to be an index of vascular myopathy. Measurements of the rate of O2 consumption (JO2), lactate production (Jlac), and isometric force in porcine coronary arteries were made under conditions known to alter both active force (delta Po) and Na+-K+ transport. As previously reported, JO2 was strongly correlated with delta Po; Jlac, however, was correlated with conditions that alter Na+-K+ transport. Under conditions known to inhibit Na+-K+ transport (10(-5) M ouabain, absence of extracellular K+ or Na+), Jlac was inhibited even though delta Po and JO2 were increased. The coupling of Na+-K+ transport with aerobic glycolysis was not dependent on tonicity or the major anion species, nor was it an effect simply on tissue lactate permeability as indicated by studies of tissue lactate content. Metabolic measurements made at similar levels of delta Po indicate that Jlac is markedly inhibited by ouabain, whereas JO2 shows little effect. Thus the unusual aerobic glycolysis observed in vascular smooth muscle appears to be linked to Na+-K+ transport processes and not to some nonspecific metabolic deficiency. Experiments on both systemic and pulmonary arteries from rat, rabbit, dog, and pig indicate that these results are not limited solely to porcine coronary vessels.

1. Basal and recovery O2 consumption, delatO2, in frog sartorius muscles at 0 degrees C were measured with a polarographic electrode. Reproducible observations were made with the same muscle over many hours. 2. The experimental records had an exponential form except for the early phases of recovery following a single isometric tetanus. Diffusion of O2 within the muscle was adequate to account for this deviation from an exponential time course of recovery. The time constant of the recovery O2 consumption increased with the duration of tetanic stimulation from 5 to 20 sec. 3. Lactate synthesis was measureable in unstimulated aerobic muscles and increased in proportion to total O2 consumption as long as the muscle did not lack O2. The contribution of glycolysis to the total chemical energy production during recovery was 6-9%; for hypoxic muscles it was greater. 4. The resynthesis of phosphorylcreatine and the decrease in inorganic phosphate and free creatine following a tetanus showed an exponential time course similar to recovery O2. Initial concentrations were re-attained within 60 min following a 20 sec tetanus. 5. We conclude that recovery O2 consumpation is a useful and accurate measure of the net chemical energy utilization for a single contraction.

The isomyosin composition in left and right ventricles from aldosterone-salt-treated hypertensive rats and from vehicle-infused and aldosterone-infused normotensive control rats was compared. A significant incremental increase (20%) in the percentage of V3 isomyosin and parallel decrease in the percentage of V1 isomyosin occurred in both left and right ventricles from aldosterone-salt-treated animals compared with those in normotensive vehicle-infused controls. No change in the ventricular isomyosin distribution was observed in animals infused with aldosterone without salt, which indicates that aldosterone does not directly affect the ventricular isomyosin composition. The changes in left ventricular isomyosin composition were accompanied by significant left ventricular hypertrophy (38%; p less than 0.05), whereas no hypertrophy was observed in the right ventricle. Plasma thyroxine levels were significantly lower in aldosterone-salt-treated rats (3.7 +/- 0.6 micrograms/dl; p less than 0.05) than in normotensive vehicle-infused (6.0 +/- 0.7 micrograms/dl) or aldosterone-infused (6.7 +/- 0.3 micrograms/dl) controls. These results indicate that factors such as alterations in thyroid status or a volume overload component of this hypertensive model, in addition to increased systolic blood pressure, may contribute to a biventricular shift in isomyosin composition in the aldosterone-salt model of hypertension.

Vascular smooth muscle is characterized by a high rate of aerobic lactate production, which may be altered independently of oxidative phosphorylation. This finding suggested a cytoplasmic compartmentation of metabolism. Exogenous glucose was found to be the sole precursor of aerobic glycolysis under unstimulated conditions. Although tissue depolarization with high K+ resulted in a substantial reduction of endogenous glycogen, exogenous glucose remained the sole precursor of aerobic lactate production. These data showed unequivocally that carbohydrate metabolism is compartmentalized in vascular smooth muscle.

Early investigations into the nature of the coupling between energy transduction and metabolism in smooth muscle, particularly from the laboratories of Bülbring and Lundholm, suggested that specific metabolic pathways could independently supply energy for ion transport and actin-myosin interactions. Subsequent work has solidified the concept that oxidative phosphorylation is specifically coupled to tension generation and maintenance, whereas, aerobic glycolysis is not only a vital characteristic of smooth muscle metabolism, but also is likely to be independently coupled to Na-K transport at the plasmalemma. The independence of oxidative and glycolytic metabolism is reflected as a compartmentation of carbohydrate metabolism in the porcine carotid artery. The coupling of these independent metabolic pathways with specific energy utilizing processes, indicates a means by which energy production and transduction can be closely and efficiently regulated. The coupling of glycogenolysis to mitochondrial respiration may have evolved as a direct response to the energetic needs of VSM. That is, the large glycogenolytic response in the initial minutes of stimulation may be necessary to maximize the cellular production of ATP during the presteady state. Likewise, the coupling between aerobic glycolysis and Na-K transport indicates a sensitive and efficient means of coordinating energy metabolism with ion transport at the membrane level. Additionally, the regulation of substrate supply, i.e. glucose transport, also may be closely coordinated with changes in ion transport. One may speculate that alterations in the microenvironment of each compartment can independently regulate intermediary metabolism and therefore allow the cell to quickly and efficiently respond to localized stimuli. Thus, stimulation of Na-K transport could effectively regulate energy production at the membrane level without mobilizing or competing with the energy transduction of other cellular processes. This compartmentation of energy utilization may be highly advantageous, since oxidative metabolism is closely coordinated with mechanical activity and therefore regulation of blood flow. Future investigations will attempt to elucidate which intracellular signals which are responsible for the regulation of these functionally independent compartments of energy metabolism and transduction in VSM. In more general terms, our findings provide a basis from which future questions concerning the regulation of cellular metabolism must be directed. The cellular cytoplasm can no longer be envisioned as a homogeneous compartment, but rather a complex array of functional subcompartments which may be individual

The hypothesis addressed in this study was that for every experimental condition, learning with awareness would occur. An experiment was conducted with use of a collating task that incorporated the awareness question into the design investigating the change in performance quality and quantity. Statistical evaluation of Dulany's awareness questionnaire suggested general unawareness of attempted verbal operant conditioning. There is some evidence suggesting that an actual change in performance quality and quantity is accompanied by awareness with use of operant conditioning procedures.