Circadian timekeeping in hyperactive and hypertensive inbred rat strains

1996 ◽  
Vol 271 (3) ◽  
pp. R787-R796 ◽  
Author(s):  
A. M. Rosenwasser ◽  
M. W. Pellowski ◽  
E. D. Hendley

Inbred strains have been used to study genetic and physiological relationships among different aspects of circadian timekeeping, as well as relationships between circadian rhythmicity and other strain-specific traits. The present study characterized several features of circadian timekeeping in genetically hyperactive (WKHA) and genetically hypertensive (WKHT) inbred strains, derived from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. WKHAs and WKHTs differed in free-running period, steady-state entrainment to light-dark cycles, and photic phase shifting, and relationships among these measures were consistent with previous studies of species, strain, and individual differences. Because both WKHTs and SHRs show short circadian periods relative to their respective comparison strains, this trait may cosegregate genetically with hypertension. In contrast, because WKHAs and SHRs show similar photic entrainment and phase shifting, these circadian functions may cosegregate with open-field hyperactivity. Finally, because neither WKHAs nor WKHTs show the SHR's excessive levels of home-cage running wheel activity, this trait is not related to either hypertension or open-field activity. Further work would be required to elucidate specific genetic and/or physiological linkages among these variables.

1993 ◽  
Vol 265 (6) ◽  
pp. R1304-R1310 ◽  
Author(s):  
N. Castanon ◽  
E. D. Hendley ◽  
X. M. Fan ◽  
P. Mormede

The behavioral and neuroendocrine reactivity to a novel environment (open field) and the adrenocorticotropic hormone (ACTH)/corticosterone response to a corticotropin-releasing factor (CRF) challenge were measured in 2-mo-old rats from four inbred strains derived from the Wistar-Kyoto rat: spontaneously hypertensive rats (SHRs), hypertensive and behaviorally hyperactive to novelty; WKY, neither hypertensive nor hyperactive; WKHA, hyperactive but normotensive; and WKHT, only hypertensive. The ACTH response to CRF was much lower in SHRs than WKYs, this reduced reactivity being clearly associated with the hyperactivity trait, since it was present in the WKHA and absent in the WKHT strain. On the other hand, the ACTH/corticosterone response to a psychological stimulus (open field) could not clearly discriminate the four strains. The largest difference was found in the prolactin response. Post-open-field levels were much lower in the WKHA (27.11 +/- 4.69 ng/ml) than in the parent WKY strain (83.65 +/- 6.84 ng/ml), the hypertensive strains having intermediate levels (WKHT: 58.05 +/- 7.65 ng/ml; SHR: 64.13 +/- 7.19 ng/ml). Other differences were also found in the levels of aldosterone and renin activity. These results indicate that these strains are an excellent model to study neuroendocrine correlates of hypertension and hyperactivity, which are associated in the SHR strain and may be of interest for the study of the association between neuroendocrine and behavioral characteristics.


1991 ◽  
Vol 261 (2) ◽  
pp. H583-H589 ◽  
Author(s):  
E. D. Hendley ◽  
W. G. Ohlsson

Two new strains of inbred rats have been developed. One, WKHA, exhibits hyperactivity, and the other, WKHT, exhibits hypertension. Both of these traits are expressed in the SHR. By crossing spontaneously hypertensive rats (SHRs) with Wistar-Kyoto (WKY) controls, followed by recombinant selected inbreeding, we succeeded in genetically separating the hyperactivity from the hypertension in two new strains. Longitudinal studies indicate a persistence of hypertension without hyperactivity in WKHTs, and hyperactivity without hypertension in WKHAs, over at least 1 year. Ventricular enlargement, another characteristic of SHRs, was observed in adult WKHTs after the onset of hypertension; however, ventricles were already enlarged in normotensive WKHAs at 6 wk. The emergent behavioral profile of WKHAs indicates that they retain the hyperactivity trait and hyperreactivity to stress, and not some of the other behaviors of SHRs, such as poor habituation. Studies in WKHTs suggest that they are an improvement over SHRs as a model of genetic hypertension as they lack some prominent behavioral abnormalities. Nevertheless, the four genetically related strains (WKHA, WKHT, SHR, and WKY), used together, are considered most appropriate for seeking correlations of biological differences with either hypertension or hyperactivity.


1999 ◽  
Vol 277 (3) ◽  
pp. R812-R828 ◽  
Author(s):  
B. Pitrosky ◽  
R. Kirsch ◽  
A. Malan ◽  
E. Mocaer ◽  
P. Pevet

Daily administration of melatonin or S20098, a melatonin agonist, is known to entrain the free-running circadian rhythms of rats. The effects of the duration of administration on entrainment were studied. The animals demonstrated free-running circadian rhythms (running-wheel activity, body temperature, general activity) in constant darkness. Daily infusions of melatonin or S20098 for 1, 8, or 16 h entrained the circadian rhythms to 24 h. Two daily infusions of 1 h (separated by 8 h) entrained the activity peak within the shorter time interval. The entraining properties of melatonin and S20098 were similar and were affected neither by pinealectomy nor by infusion of 1- or 8-h duration. However, with 16-h infusion, less than half of the animals became entrained. Once entrained, the phase angle between the onset of infusion and the rhythms (onset of activity or acrophase of body temperature) increased with the duration of infusion. Before entrainment, the free-running period increased with the duration of infusion, an effect that was not predictable from the phase response curve.


Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 230-239 ◽  
Author(s):  
Sonoko Ogawa ◽  
Johnny Chan ◽  
Jan-Åke Gustafsson ◽  
Kenneth S. Korach ◽  
Donald W. Pfaff

Abstract Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERα and ERβ, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERα (αERKO) or the ERβ (βERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male αERKO mice, running wheel activity was not different from that in corresponding wild-type (αWT) mice in placebo control groups. In both females and males it was increased by EB only in αWT, not αERKO, mice. In βERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in βWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in βERKO females compared with βWT females. Before EB treatment, gonadectomized αERKO female were significantly less active than αWT mice in open field tests, whereas βERKO females tended to be more active than βWT mice. In male mice there were no effect of ERα or ERβ gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERα, not the ERβ; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured.


2021 ◽  
Vol 12 ◽  
Author(s):  
Annemarie Wolf ◽  
Hanna Sarah Kutsche ◽  
Felix Atmanspacher ◽  
Meryem Sevval Karadedeli ◽  
Rolf Schreckenberg ◽  
...  

Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.


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