COMPLEX CHANGES IN THE ENERGY HOMEOSTASIS OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR)
Mikó A., Füredi N., Tenk J., Pétervári E., Balaskó M.
Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary
INTRODUCTION
Spontaneously hypertensive rats (SHR) have been developed as an animal model for the study of human hypertension. This rat strain is characterized by enhanced sympathetic tone, by reduced food intake (FI) and attenuated body weight (BW) development. These rats cannot reach the BW of normally fed controls even on a high-calorie diet. Increased sensitivity of the catabolic melanocortin (MC) system has also been observed in SHR rat strain that may contribute to their hypertension via enhancement of the sympathetic tone. These observations suggest complex changes in the regulation of energy balance in SHR rats.
METHODS
Parameters of energy balance [FI, BW, core temperature (Tc), heart rate (HR, indicating metabolic rate)] of 6- month-old male SHR rats were recorded in a biotelemetric system (MiniMitter) during a 7-day (1μg/μl/h) intracerebroventricular infusion of alpha-melanocyte-stimulating-hormone (alpha-MSH). In other rats adaptation to a 5-day fasting and following re-feeding was observed in the same system. Age- and BW-matched controls were used. One way ANOVA and repeated measures ANOVA were used for the statistical analysis of the data.
RESULTS
Spontaneous FI of SHR animals was smaller than that of controls. During a 5-day fasting BW of all rats decreased similarly. However, SHR rats were unable to regain their original BW by the 5th day of re-feeding unlike controls, due to a reduction in
their compensatory
overeating (Figs. 1,2). At the same time their adaptive suppression of Tc and HR were reversed sooner during re-feeding (Fig. 3).
Exogenous alpha-MSH- induced FI- and BW- reductions were similar in all rats, but the effects were of shorter duration in SHR rats (Figs. 4,5). Elevations in HR and Tc were reduced and appeared during the active (nighttime) instead of the inactive (daytime) period (Figs. 6,7,8,9).
TIME (days)
-6 -4 -2 0 2 4 6 8 10
BW (g)
-100 -80 -60 -40 -20 0 20 40
control 3 months control 6 months SHR 6 months
STARVATION REFEEDING
*
*
-3 -2 -1 0 1 2 3 4 5 6 7 8 9
ÉHEZÉS
TIME (days)
FI (g)
0 5 10 15 20 25 30 35
SHR 6 months control 6 months control 3 months
*
*
*
* # # #
STARVATION
-3 -2 -1 0 1 2 3 4 5 6 7 8 9 260
280 300 320 340 360
control SHR
HR (1/min)
TIME (days) STARVATION
* * *
-3 -2 -1 0 1 2 3 4 5 6 7
FI (g)
0 10 20 30
saline
MSH
TIME (day)
-3 -2 -1 0 1 2 3 4 5 6 7
BW (g)
-20 -15 -10 -5 0
INFUSION
*
*
35.0 35.5 36.0 36.5 37.0 37.5 38.0
saline
Tc (oC) MSH
TIME (day) INFUSION
-3 -2 -1 0 1 2 3 4 5 6 7
*
HR (1/min)
*
280 300 320 340 360 380
saline
MSH
TIME (day) INFUSION
-3 -2 -1 0 1 2 3 4 5 6 7
*
Fig. 4
Changes in FI and ∆BW (compared to the initial BW) during -MSH or saline infusion
in 6 months old control rats.
Fig. 1
∆BW (compared to the initial body weight) changes in the SHR and control groups during
starvation and refeeding.
Fig. 2
FI (food intake) changes in SHR and control groups before starvation and upon
refeeding.
Fig. 3
Starvation and refeeding induced HR (heart rate)
changes in SHR and 6 month-old control rats.
Fig. 5
Changes in FI and ∆BW (compared to the initial BW)
during -MSH infusion in 6 months old SHR and their age
matched control group.
Fig. 6
Changes in Tc during -MSH or saline infusion in control
rats.
Tc (oC)
-3 -2 -1 0 1 2 3 4 5 6 7 35.0
35.5 36.0 36.5 37.0 37.5 38.0
control
-MSH INFUSION SHR HR(1/min)
TIME (day)
*
280 300 320 340 360 380
control
-MSH INFUSION SHR
-3 -2 -1 0 1 2 3 4 5 6 7
CONCLUSION
Higher intrinsic MC activity contributing to the catabolic shift in the energy balance of SHR rats could not be further stimulated by exogenous alpha-MSH. However, a higher MC-activity may have contributed to the maladaptation to fasting-
induced re-feeding. OTKA PD84241, PTE AOK-KA-34039-02/2010, 34039/KA-OTKA/11-01
Fig. 7
Changes in Tc during -MSH infusion in SHR vs. control rats.
Fig. 8
Changes in circadian rhythm of HR during -MHS or saline
infusion in control rats.
Fig. 9
Changes in the circadian rhythm of HR during -MSH infusion in
SHR vs. control rats.
*
-2 -1 0 1 2 3 4 5 6 7
FI(g)
0 10 20 30
control SHR
TIME (days)
-2 -1 0 1 2 3 4 5 6 7
BW (%)
-6 -4 -2 0 2
MSH INFUSION
*
AIMS
To investigate such alterations, adaptation of SHR rats to fasting and their responsiveness to a centrally applied MC agonist were studied.
