Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intermittent infusions of dobutamine were studied in young normal male subjects during a period of bedrest deconditioning to determine whether this synthetic catechol affects physical conditioning processes in humans. 24 volunteers were placed at bedrest and randomized to daily 2-h treatments of saline infusions (control), dobutamine infusions, or maintenance exercise (control). Exercise, hemodynamic, and metabolic studies were performed at base line and at the termination of the 3-wk treatment period. Maximal exercise (duration, oxygen consumption, and workload) fell for the saline group and remained unchanged for the dobutamine and exercise groups. Hemodynamics during exercise were maintained the same as pretreatment base line for the dobutamine and exercise groups, whereas stroke volume and cardiac output dropped and heart rate rose for the saline group. The metabolic profile showed an increased blood lactate response at rest and during submaximal exercise after 3 wk of bedrest for the saline group, and essentially no change for the exercise and the dobutamine groups. Extraction of oxygen across the exercising lower limb rose for the dobutamine group, as did the activity of the skeletal muscle oxidative enzymes, citrate synthetase, and succinate dehydrogenase. In contrast to the exercise control group, the saline and dobutamine groups developed orthostatic hypotension, tachycardia, and accentuation of the renin-aldosterone response over the 3-wk treatment period; for the saline group, this is best explained by the observed fall in blood volume and for the dobutamine group, by the blunting of vascular vasoconstrictive responses. During a period of bedrest deconditioning in humans, infusions of dobutamine maintain many of the physiologic expressions of physical conditioning.
 ...
PMID:Prevention of bedrest-induced physical deconditioning by daily dobutamine infusions. Implications for drug-induced physical conditioning. 393 70

Small gene effects influence complex phenotypes in a context dependent manner. Here we evaluated whether increasing dosage of the angiotensin I converting enzyme (Ace) gene influence exercise-induced cardiac hypertrophy. Mice harboring one, two, three, and four copies of the Ace gene were assigned to sedentary (S1-4) and swimming exercise-trained (T1-4) groups (1.5 h twice daily, 5 days/wk, 4 wk). Exercising resulted in comparable bradycardia and elevated skeletal muscle citrate synthase activity, while blood pressure remained unchanged. Left ventricle mass index and cardiomyocyte diameter were similar among sedentary mice and the magnitude of their increase associated to exercising was not influenced by the Ace genotype (T1: 12.6 and 17.9%, T2: 15.2 and 13.8%, T3: 16.9 and 20%, T4: 17 and 19%, respectively). Plasma renin activity (PRA) levels were higher in one vs. three or four copies mice (4.89 +/- 0.5 vs. 2.43 +/- 0.6 and 2.12 +/- 01.1 ng/ml Ang I, P < 0.05), while cardiac ACE activity was higher in three vs. two or one copy mice (5,946 +/- 590.8 vs. 2,951.5 +/- 328.3 and 3,504.1 +/- 258.9 microF x min(-1) x ml(-1), P < 0.05). With exercise, PRA remained unchanged in each group, while cardiac immunostaining for Ang II reached comparable levels. In summary: 1) exercise training led to similar aerobic adaptation regardless of the Ace genotype, and 2) higher number of Ace gene copies per se, which alters cardiac ACE activity, did not influence basal cardiac mass or, most importantly, the magnitude of swimming-induced cardiac hypertrophy. Collectively, these data indicate that small isolated genetic disturbances in ACE cardiac levels can be well compensated under physiological perturbations.
 ...
PMID:Small gene effect and exercise training-induced cardiac hypertrophy in mice: an Ace gene dosage study. 1692 72