Modification of catecholamine-induced changes in heart function by food
restriction in rats.
McKnight KA, Rupp H, Beamish RE, Dhalla NS
Division of Cardiovascular Sciences, St. Boniface General Hospital Research
Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
In view of the common practice of dieting for weight reduction, the
influence
of severe food restriction (about 25% of ad libitum intake) on adrenergic
mechanisms was studied. Cardiac norepinephrine and epinephrine concentrations
as well as plasma norepinephrine levels, were increased upon feeding
a
restricted diet to rats for 14 days in comparison with control rats
that
ingested about 30 g food/ day. Bradycardia as well as characteristic
electrocardiographic abnormalities, including prolongation of the QRS
and QT
intervals, were observed in food-restricted rats. Diet-restricted rats
did not
develop ventricular arrhythmias in response to epinephrine injections
as
readily as control rats. Depression in both + dP/dt and -dP/dt of the
heart in
situ as well as reductions in the inotropic responses to epinephrine
were
evident in diet-restricted rats. Beta-adrenergic binding studies revealed
a
significant decrease in receptor density, but the dissociation constant
for
binding was also depressed in the food-restricted rat heart. Downregulation
of
the beta-adrenergic receptors in the heart may explain the lack of
an
epinephrine-induced increase in contractile force development as well
as
arrhythmias in food-restricted rats. These data demonstrate that severe
food
restriction has marked effects on adrenergic mechanisms and heart function,
and
thus some caution should be exercised at early periods of this therapy
for
weight reduction.