Exercise Improves Blood Flow Dynamics, Survival in Rat Model

Heart cells in sedentary rats saw reduction in protein that aids glucose uptake

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Two weeks of aerobic exercise improved blood flow parameters and survival in a rat model of pulmonary arterial hypertension (PAH), and altered the energy usage of cells in the heart, a new study reports.

“Our data support the beneficial effect of exercise training in this clinical setting, as two weeks of training prevented diastolic dysfunction … and improved survival,” the researchers wrote.

The study, “Exercise training counteracts the cardiac metabolic remodelling induced by experimental pulmonary arterial hypertension,” was published in the Archives of Biochemistry and Biophysics.

A feature of PAH is high pressure in the vessels that carry blood to the lungs, which puts strain on the heart, especially that part responsible for pumping blood to the lungs, the right ventricle (RV).

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Aerobic exercise has many cardiovascular health benefits and is generally recommended for people with PAH. Little is known about how aerobic exercise affects the health of the RV in PAH, however.

Scientists in Portugal induced PAH in male rats with a chemical called monocrotaline, a model that “reasonably mimics RV changes found in the human condition,” the researchers said. They noted this model also has a very high mortality rate.

The rats were either maintained under sedentary conditions or ran on a treadmill one hour a day for two weeks. The PAH rats that exercised showed improvements in survival compared to their sedentary counterparts.

Analyses of blood flow dynamics showed sedentary PAH rats had marked diastolic dysfunction — that is, abnormal pressure between heart beats. Rats that exercised did not display this, indicating “exercise training was capable to prevent diastolic dysfunction,” the researchers wrote.

Analyses of the physical structure of the rats’ hearts generally did not reveal differences between the exercise and sedentary groups. There were some differences in the activity of metabolic proteins, however.

Sedentary PAH rats’ heart cells showed a marked reduction in the expression of GLUT4, a protein needed to bring glucose — the sugar molecule used by most cells to generate energy — into the cell. GLUT4 levels were comparatively increased in rats that exercised.

“Our data points to a decreased uptake of glucose in the RV of sedentary [PAH] rats, given by the diminished content of GLUT4 transporter,” the researchers wrote.

Cells in the RV usually rely on fatty acids as a main energy source, but they typically undergo a metabolic shift and start requiring more glucose for energy in PAH.

Exercise didn’t affect fatty acid usage in PAH rats, but it did increase the activity of a protein called LDH that’s involved in “burning” glucose to generate usable energy by oxidizing it into lactate, other analyses showed.

“The improved cardiac phenotype promoted by two weeks of treadmill exercise was related to an increased uptake of glucose to cardiomyocytes [heart muscle cells] through GLUT4 followed by its oxidation to lactate,” the researchers wrote.

Exercise didn’t change the number of energy-generating mitochondria inside heart cells, but the researchers noted an increase in some genes related to mitochondrial growth after exercise.

“The underlying molecular mechanisms of the cardioprotective effects [of exercise in PAH] are not well-established,” the scientists said, noting their study “adds new molecular insights, mostly at the metabolic level.”

“Overall, our study shows that only two weeks of exercise training performed after disease diagnosis slows the progression of the disease by modulating the energetic substrate utilization of the RV towards increased rate of glucose oxidation,” they said.

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