Effect of glycerol-induced acute renal failure and di-2-ethylhexyl phthalate on the enzymes involved in biotransformation of xenobiotixs.

The effects of di-(2-ethylhexyl)-phthalate (DEPH) on the levels of cytochrome P-450 and b5 monooxygenases were studied in the rat kidney and liver in acute renal failure induced by glycerol. Intramuscular injection of glycerol (50%,10 ml x kg(-1)) to rats produced proximal tubular damage and acute renal failure. The indicators of renal function, serum urea and creatinine significantly increased (480 and 350 percent, respectively). In control and glycerol-treated animals DEPH had no significant effect on the concentrations of serum urea and creatinine. Twenty-four hours after glycerol injection the total amount of cytochrome P-450 and b5 significantly decreased in renal but increased in liver microsomal fractions. Moreover, 48 and 72 hours after glycerol injection the level of cytochrome P-450 and b5 significantly increased in both organs. A single dose of DEPH (2 ml x kg(-1), i.p.) also elevated the total cytochrome P-450 and b5 in control animals. This enhancing effect of DEPH was additive to that of glycerol in glycerol-induced acute renal failure. These results indicate that DEPH and glycerol evoked pathological changes may affect the metabolism of xenobiotics plus endogenous hormones in the liver and in kidney.

Comparative force-velocity relation and analyses of myosin of dog atria and ventricles.

The isolated muscle and purified myofibrillar proteins of canine atria and ventricles were compared relative to force-velocity relations and rate of adenosine 5'-triphosphatase (ATPase) activity as a function of calcium concentrations. The maximal stress development of isolated trabeculae of canine atria was similar to that of canine right ventricular papillary muscles when analyzed at saturating calcium concentrations (7.5 mM); however, stress was less in the atria when studied at normal calcium concentrations (2.5 mM). The maximal velocity of shortening of atrial trabeculae was about 2.3 times higher than that of ventricular muscle. Regulated actomyosin characterized from the myofibrillar proteins of the two tissues gave directionally similar calcium sensitivity. The maximum velocity of shortening for actin-activated atrial myosin of the dog was approximately 1.8 times higher when the latter was analyzed as a function of actin concentration. Both maximal tension of isolated muscle and regulated actomyosin ATPase activity were dependent on calcium concentration.

Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster.

We attempted to alter the inherited myocardial damage and loss of contractility of the cardiomyopathic Syrian hamster (strain U-MX7-1) by giving cardiac drugs that altered intracellular calcium and myocardial workload. Thirty-seven 21-day-old cardiomyopathic and thirty-seven 21-day-old normal hamsters were divided into five groups each: verapamil-, propranolol-, digoxin-, hydralazine-, and saline-injected. On their 90th day of life, the hamsters were killed. Of the five cardiomyopathic groups, only verapamil reduced myocardial damage. When both "control" and cardiomyopathic hamsters were treated with saline, digoxin, or propranolol, the cardiomyopathic hamsters had significantly less contractile force, maximal rate of force development, and maximum velocity of unloaded shortening. When both groups were treated with verapamil or hydralazine, there were no significant group differences in the indices of contractility. However, when saline-treated cardiomyopathic hamsters were compared with drug-treated cardiomyopathic hamsters, only verapamil preserved myocardial contractility. There was also a weak correlation between the Vmax and the actin-activated ATPase activity of the cardiomyopathic hamsters (r = 0.63, P less than 0.001). We conclude that verapamil helped protect the myocardium of genetically cardiomyopathic hamsters against structural damage, and helped preserve myocardial contractility.

Experimental investigations on the hypokinesis of skeletal muscles with different functions, VIII. Effect of plaster-cast immobilization on the contractile properties of rat skeletal muscles with different functions.

The plaster-cast immobilization of the right hind limbs of rats has been investigated. Examinations were performed on the changes in weight of both types of skeletal muscles, i.e. the fast and the slow ones, the m. extensor digitorum longus and the m. gastrocnemius on the one hand, and the m. soleus on the other. The most significant loss in weight was observed in the gastrocnemius muscle. The ATP-Ca2+-induced isometric tension as well as the speed of contraction of glycerine-treated myofibrillar preparations considerably decreased as a result of 28-day immobilization. The most marked change was observed in the soleus muscle. There was a similar decrease in the specific activity of myofibrillar myosin ATPase prepared from immobilized muscles. The specific activity of K+-EDTA myosin ATPase did not change.

Effect of neurectomy on nuclease activity in skeletal muscles of rats.

Author followed up the activity of the three enzymes involved in the catabolism of nucleic acids--acid deoxyribonulease (DNase II), alkaline ribonuclease (RNase I), and acid ribonuclease (RNase II)--in the denervated gastrocnemius and soleus muscles of rats for 28 postoperative days. The activity of both acid nucleases increased in both types of denervated muscles, compared with the respective controls. Up to the 14th postoperative day, the activity excess of both acid nucleases was more significant in the m. gastrocnemius than in the m. soleus. The RNase I ran below the control activity during the whole period in the m. soleus and up to the 14th day in the m. gastrocnemius. The role of nucleases and nuclease inhibitors in the changes of nucleic acid catabolism in neurogenic muscular atrophies is discussed.

Experimental investigations on hypokinesis of skeletal muscles with different functions. I. Changes in muscle weight, protein and contractile properties.

In New Zealand white rabbits the right hind limb was immobilized in full extension with a plaster cast. The free left hind limb served as control. The masses of both the tetanic m. gastrocnemius and the tonic m. soleus considerably decreased as a consequence of immobilization for 5, 10, 14, 25 or 42 days. The decrease was more marked for the m. soleus. The water content of the muscle did not change substantially in the course of the atrophy. The total protein and myofibrillar protein contents of the immobilized muscles fell significantly. The tonic m. soleus atrophised sooner and was more extensive than the m. gastrocnemius. Superprecipitation of the myofibrillar proteins of the immobilized muscles decreased by 20-25% compared to the controls. The experimental model is considered suitable for further biochemical and ultrastructural investigations relating to the development of atrophy and to regeneration.

Experimental investigations on hypokinesis of skeletal muscles with different functions, II. Quantitative changes in the nucleic acids.

The effect of hypokinesis on the quantitative changes in the nucleic acids was studied in functionally different muscles of rabbits on the 5th, 10th, 14th and 28th days following plaster cast immobilization of the limbs. As a consequence of the immobilization, the total amount of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) decreased in both the tonic and the tetanic nuscles. The decrease was more marked in the tonic muscles. As a result of the hypokinesis, the RNA/DNA ratio increased in the m. gastrocnemius, and decreased in the m. soleus. The plaster cast immobilization has a greater effect on the homoeostasis of the nucleic acids of the tonic muscles than in the case of the tetanic muscles.