Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.
Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.
Durgan
David J
DJ
United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Houston, Texas, USA.
Moore
Michael W S
MW
Ha
Ngan P
NP
Egbejimi
Oluwaseun
O
Fields
Anna
A
Mbawuike
Uchenna
U
Egbejimi
Anu
A
Shaw
Chad A
CA
Bray
Molly S
MS
Nannegari
Vijayalakshmi
V
Hickson-Bick
Diane L
DL
Heird
William C
WC
Dyck
Jason R B
JR
Chandler
Margaret P
MP
Young
Martin E
ME
D000818:Animals; D002940:Circadian Rhythm; D005947:Glucose / Q000378:metabolism; D050261:Glycogenolysis; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012107:Research Design; D013997:Time Factors
D019301:Oleic Acid; D019344:Lactic Acid; D005947:Glucose