Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR(-/-) mice: a paradox of preserved V'O2max and exercise capacity despite coronary atherosclerosis.
We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR(-/-) mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V'O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR(-/-) mice V'O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR(-/-) mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR(-/-) mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V'O2max and exercise capacity.
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
M
M
Wojewoda
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences Krakow, Poland.
U
U
Tyrankiewicz
Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
P
P
Gwozdz
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences Krakow, Poland.
T
T
Skorka
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences Krakow, Poland.
M
M
Jablonska
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences Krakow, Poland.
A
A
Orzylowska
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences Krakow, Poland.
K
K
Jasinski
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
A
A
Jasztal
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
K
K
Przyborowski
Department of Human Nutrition, Faculty of Food Technology, University of Agriculture in Krakow, Krakow, Poland.
R B
RB
Kostogrys
Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Krakow, Poland.
J A
JA
Zoladz
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.|Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
S
S
Chlopicki
D000818:Animals; D001783:Blood Flow Velocity; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004280:Dobutamine; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D011973:Receptors, LDL / Q000235:genetics; D013312:Stress, Physiological / Q000502:physiology*
D011973:Receptors, LDL; D009569:Nitric Oxide; D004280:Dobutamine; D011464:Epoprostenol