Synchronization of proximal intratubular pressure oscillations: evidence for interaction between nephrons

Previous studies in rat kidneys have demonstrated that oscillations in the proximal intratubular pressure are a prominent feature of the tubulo-glomerular feedback mechanism (TGF) operating during free flow conditions. The purpose of the present study was to investigate whether a subpopulation of synchronized, interacting nephrons could be detected. In group A nephrons, i.e., nephrons with a high probability of having their afferent arterioles arising from the same interlobular artery, 29 out of 33 pairs of nephrons were found to show synchronized pressure oscillations. In group B nephrons, not expected to have this common origin of their afferent arterioles, only 1 out of 23 pairs was found to be synchronized. The standard deviation of the frequency differences was 0.063 cycles per minute in group A nephron pairs and 0.202 cycles per minute in group B pairs (p<0.05), showing the greater homogeneity in frequency in group A. Furthermore, nephrons having synchronized pressure oscillations were found to interact with each other. Thus, perturbation of the proximal tubular pressure oscillations in one nephron by loop microperfusion affected the amplitude of the pressure oscillations in the non-perfused nephron; and reactivation of pressure oscillations in one nephron was followed by reactivation of oscillations in the non-perfused nephron. Thus, the present results show that there exists a well defined subpopulation of nephrons, in which the TGF-mediated proximal pressure oscillations are synchronized. This synchronization is a result of interaction between the different nephrons. It is suggested that the interaction is a consequence of cross-talk between the TGF signals from the different nephrons concerned, transmitted along the afferent arterioles, and probably also along a part of the interlobular artery.     

Central blood volume in spontaneously hypertensive rats and Wistar-Kyoto normotensive rats

Central blood volume and total blood volume were determined in spontaneously hypertensive rats and Wistar Kyoto rats at two ages, 6 and 12 weeks, representing ‘borderline’ hypertension and early ‘established’ hypertension, respectively. A technique was used where plasma and erythrocyte indicators were injected into conscious rats. Blood volume in the cardiopulmonary compartment, present in the ‘resting’ awake steady-state, could then be estimated by sudden freezing of the entire rat. 12 week-old spontaneously hypertensive rats showed a decreased total blood volume, while the fraction of blood contained in the cardiopulmonary area was significantly increased compared with that of normotensive Wistar Kyoto rats. In 6-week-old spontaneously hypertensive rats, total blood volume was only marginally decreased but also here a tendency towards centralization of the blood was seen. Thus, along with the development of hypertension in the spontaneously hypertensive rat their decreasing blood volume tends to become increasingly centralized to the cardiopulmonary area. Both neurohormonal influences and structural wall changes in the low-pressure capacitance side may contribute to this.     

Circulating and local visfatin/Nampt/PBEF levels in spontaneously hypertensive rats,stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats

Visfatin (also known as nicotinamide phosphoribosyltransferase and pre-B cell colony-enhancing factor) is a multifunctional protein. Visfatin has been reported to be involved in several biological processes in the cardiovascular system, . However, the role of visfatin in hypertension is still unclear. In this study, we examined the circulating and local adipose visfatin levels in spontaneously hypertensive rats (SHR), stroke-prone spontaneously hypertensive rats (SHR-SP), and in their normotensive control Wistar-Kyoto (WKY). SHR and SHR-SP rats exhibited lower body weight, lower fat tissue and hypolipidemia. No differences of serum visfatin levels were observed in SHR/SHR-SP and WKY. Serum visfatin levels did not correlate to serum glucose, lipids, insulin, and fat pad weights, but significantly correlated to weights of skeletal muscle. Visfatin expression in visceral fat tissue was slightly lower in SHR-SP compared with that in WKY. Moreover, there were no significant differences of visfatin expression in skeletal muscles among WKY, SHR and SHR-SP. Finally, visfatin protein was detected in L6 rat skeletal muscle cell culture medium, indicating that visfatin was secreted from skeletal muscle cells. Thus, our results may provide useful information for understanding the characteristic of visfatin in hypertensive models, and support the view that visfatin may be a myokine.     

Preweanling behavioral development in spontaneously hypertensive, borderline hypertensive, and Wistar-Kyoto normotensive rats

Preweanling physical and behavioral development was studied in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and Wistar-Kyoto normotensive (WKY) rat pups. Measures of physical development included body weight, onset of various morphological landmarks, and speed of surface righting. Behavioral tests assessed locomotor development, exploratory behavior, and cliff avoidance in pups of the 3 groups. On all measures employed, SHR pups exhibited a delay in physical maturation compared to age-matched BHR and WKY pups. Results from the locomotor development test revealed that young WKY pups (ages 1-7 days) spent more time locomoting than SHR pups, with BHR times being intermediate. In contrast, older SHR pups (ages 17-30 days) displayed greater activity in an exploratory maze than WKY pups, with BHR values again intermediate. Finally, SHR pups were more behaviorally reactive in the cliff avoidance task compared to BHR and WKY pups. These group differences may be useful in understanding the development of genetic hypertension and may serve as early behavioral markers of a predisposition to cardiovascular disease.     

Strain-dependent response to cerebral ischemic preconditioning: differences between spontaneously hypertensive and stroke prone spontaneously hypertensive rats

Ischemic preconditioning (PC) is a phenomenon whereby a brief exposure to ischemia renders a tissue more tolerant to a subsequent sustained ischemic insult. Animals of the Spontaneously Hypertensive (SHR) and the Spontaneously Hypertensive Stroke-Prone (SHR-SP) rat strains produce cerebral infarcts that are larger and more reproducible in size than infarcts of normotensive rats. This study compared the effects of PC in SHR and SHR-SP rats, under the hypothesis that PC may not be as effective in the SHR-SP, a strain genetically predisposed to stroke. There were two groups per strain, with between eight and ten animals each. The Precondition group (PC) had a 10 min occlusion of the middle cerebral artery on day -1. On the same day the Sham group (Sham) received sham surgery. On day 0, both groups underwent permanent occlusion of the middle cerebral artery. The ischemic lesion was measured on day 1 using T(2)-weighted magnetic resonance imaging. Percent hemispheric infarct was significantly reduced in SHR PC vs. SHR Sham, SHR-SP PC vs. SHR-SP Sham, and SHR PC vs. SHR-SP PC. Thus, rats of the SHR-SP strain respond to PC less markedly than SHR animals. Both models may now be used to elucidate the mechanisms underlying PC.     

Pathophysiological differences between obese and non-obese spontaneously hypertensive rats.

A genetic variant of the spontaneously hypertensive rat (SHR) has been produced which becomes markedly obese as well as hypertensive, i.e. Obese/SHR weigh 800 g as against 300 g for non-obese cohorts. Serum enzymes (CPK, SGOT, SGPT and LDH) are frequently abnormally elevated, concomitantly with a high incidence of myocardial necrosis. Obese/SHR are hyperlipidaemic with severe fatty infiltration of the liver; they are hyperglycaemic with enormous islets of Langerhans and extensive beta-cell degranulation; despite elevated blood urea nitrogen (BUN) levels, they manifest little or no renal damage. Measurement of corticosterone, deoxycorticosterone (DOC) and aldosterone in Obese/SHR demonstrate marked hyper-responsiveness to moderate stress. Circulating prolactin levels are lower in Obese and non-obese/SHR compared to SHR, but Obese/SHR manifest unusually high increases incirculating prolactin levels in response to stress. Obese/SHR are hyperinsulinaemic and have subnormal growth-hormone levels. Desite mild hypertension, hyperglycaemia and hyperlipidaemia, Obese/SHR show no evidence of atheromatous change but do develop early polyarteritis nodosa. It is believed that the genetically programmed hypertension and hyperglycaemia is mediated by increased DOC, aldosterone and corticosterone production respectively, and that the obesity, hypertension, and diabetes in Obese/SHR may be likened to human Cushing''s disease.     

Patterns of behavioral development in spontaneously hypertensive rats and Wistar-Kyoto normotensive controls

We have examined the behavior of spontaneously hypertensive (SHR) rats and stroke-prone hypertensive (SP-SHR) male rats during the development and maintenance of elevated blood pressure and compared this pattern with age- and gender-matched normotensive (WKY) rats of the same Wistar-Kyoto strain as controls. Rats of each strain (n = 10/age group) were isolated in individual cages and observed for 60 min at 3,4,6,8,10, or 20 weeks of age using a scan sampling technique. At all ages SHR rats were significantly more active than WKY rats whereas SP-SHR rats were intermediate in level of activity. In a 2nd series, activity of male rats of each strain was monitored continuously for 24 hr in the home cage. No strain differences in amount or pattern of total daily activity were evident at either 4-6 or 16-18 weeks of age. These results indicate that SHR rats are more reactive to environmental change, but the intermediate level of activity of SP-SPHR rats suggests that this response is not related to the degree of blood pressure elevation,     

Tubuloglomerular feedback and autoregulation of glomerular filtration rate in Wistar-Kyoto spontaneously hypertensive rats

Experiments were done in Wistar-Kyoto spontaneously hypertensive rats (SHR) to examine the efficiency of autoregulatory adjustments of kidney and nephron filtration rate (GFR) to acute changes in blood pressure (BP) over a broad blood pressure range. When BP of the SHR was reduced from 158±7 to 118 ±3 mm Hg by aortic clamping, kidney-GFR remained unchanged from 1.19±0.11 to 1.17±013 ml·min^–1·g^–1 kidney weight (KW), respectively. Single nephron GFR (SNGFR) measured at early distal tubule sites was similarly unchanged with the same BP change, 27.9±1.5 vs. 24.9±2.1 nl·min^–1·g^–1 KW (P>0.10). Proximal and distal estimates of SNGFR were significantly different from each other at high BP (7 nl·min^–1·g^–1,P<0.025), but were not different at low BP (2.0 nl·ml^–1·g^–1,P>0.10). Studies assessing tubuloglomerular feedback activity were done with orthograde perfusion of the loop of Henle using recollections of early proximal flow rate (EPFR) as an index of change of glomerular filtration rate. A change in perfusion rate from 0 to 45 nl·min^–1 induced a reduction in early proximal flow rate of 40.5 ±4.5%. Juxtaglomerular renin activity of superficial nephrons was 36.2±4.3 in the SHR, a value insignificantly different from 23.7±4.4 ng Angiotensin II amide·0.1 ml^–1·h^–1. 5 glomeruli^–1 in normal controls (P>0.05). The SHR appears to behave as a normal animal with respect to tubologlomerular feedback and autoregulatory renal vascular adjustments. Like normal rat models, the SHR demonstrated dependence on maintenance of distal filtrate delivery to achieve single nephron GFR autoregulation.Financial support for these studies and for Dr. Ploth were made available by funds from the Deutsche Forschungsgemeinschaft     

Age-series characteristics of locomotor activities in spontaneously hypertensive rats: a comparison with the Wistar-Kyoto strain

This study was to investigate the behavioral specificities of spontaneously hypertensive rats (SHR) and compare them with Wistar-Kyoto (WKY) controls using a 1-year longitudinal study of locomotor activity. Rat locomotor activity was examined every week at 4-12 weeks of age and every month at 4-12 months of age using an Automated Digiscan Activity Monitor system. Six behavioral variables were collected and analyzed: horizontal activity (HA), total distance (TD), movement time (MT), vertical activity (VA), stereotypy count (SC), and margin time (MGT). In general, a significant weekly and monthly age-dependent change (p<0.01) in SHR was shown in the HA, TD, VA, SC and MT variables, whereas MGT showed no significant differences (p>0.05). However, except for the first observations, SHR was significantly hyperactive relative to WKY for HA, VA, TD, MT and SC (p<0.01) before 6 months of age. MGT in SHR were significantly lower than those of WKY (p<0.01) before 3 months of age. Only for VA, SHR was more hyperactive than WKY (p<0.01) and sustained for 12 months in age. From the present results, by extending the observations of locomotor activity testing from 4 weeks to 12 months of life, we were able to observe an interesting strain difference between SHR and WKY in the development pattern of spontaneous activity levels.     

Changes in brainstem and spinal adrenoceptor binding with ageing in spontaneously hypertensive and Wistar-Kyoto rats

Adrenoceptor binding in membranes prepared from the brainstem and thoracic spinal cord of male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats aged 6 and 36-40 weeks has been compared. Binding of [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [3H]dihydroalprenolol (DHA: beta-receptors) fell with age in both regions in both strains. Strain, independent of age, was also a significant determinant of binding for all three ligands in brainstem and for [3H]DHA in spinal cord. The changes in receptor binding may reflect differences in noradrenergic activity with age and between SHR and WKY rats.     

Differences in striatal spiny neuron action potentials between the spontaneously hypertensive and Wistar-Kyoto rat strains

The spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) inbred rat strains display behavioral differences characterized by relative increases and decreases in levels of activity. Both strains have subsequently been utilized as animal models of hyperactive and hypoactive behavioral traits. The etiology of these behavioral characteristics is poorly understood, but may stem from alterations in the physiology of selected neural circuits or catecholamine systems. This study investigated the cellular properties of neurons from three genetically related strains: the SHR; WKY; and Wistar (WI). In vivo intracellular recordings were made under urethane anesthesia from spiny projection neurons in the striatum, a brain area involved in behavioral activation. Results obtained from 71 spiny projection neurons indicate that most cellular properties of these neurons were very similar across the three strains. However, the amplitude and half-duration of both spontaneously occurring and current-evoked action potentials were found to be significantly different between the SHR and WKY strains with neurons from the SHR firing action potentials of relatively greater amplitude and shorter duration. Action potential parameters measured from the WI rats were intermediate between the two other strains. These differences in action potentials between two behaviorally distinct strains may reflect altered functioning of particular membrane conductances.     

Development of immunoreactive atrial natriuretic peptide in fetal hearts of spontaneously hypertensive and Wistar-Kyoto rats

Summary The development of immunoreactive atrial natriuretic peptide (ANP) was studied in fetal hearts of spontaneously hypertensive (SHR) and compared to normotensive Wistar-Kyoto (WKY) rats. While SHR fetal hearts were noticeably less developed than those of WKY at 10 and 11 days gestation, both strains showed ANP immunoreactive cells in some but not all primitive heart tubes. At 12 days additional ANP immunoreactive cells appeared in formative trabeculae of the ventricle and atrium. ANP cells were also observed in the myogenic layer of the truncus and bulbus arteriosus and their derivatives from 11 through 16 days, but not at 18 days. In both strains, there were more ANP cells in the left ventricle than in right beginning at day 13. There were no obvious strain differences in the developmental pattern and timing of ANP producing cells. However, on the day of birth, staining was reduced in hearts from some WKY newborn pups compared with hearts from SHR newborns and ventricular staining was reduced in both strains when compared to fetal hearts. These observations indicate that ANP is one of the earliest peptide hormones produced and that the predisposition to genetic hypertension does not appear to influence the development of ANP.     

Left atrial pressure in normotensive and spontaneously hypertensive rats

The left atrial pressure in adult spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control rat (NCR) was measured via chronically implanted catheters. In SHR left atrial pressure in end-expiration was more than twice as high (10.3±0.4 mmHg) as in NCR (4.6±0.3 mmHg). There was no difference in the intrapleural pressure between the two groups of rats, therefore the enhanced left atrial pressure in SHR represents a real rise in the diastolic filling pressure of its left ventricle. This is considered to be the most important compensation for the earlier reported rightward shift of the Frank-Starling curve in SHR (Hallbäck, Isaksson & Noresson 1975, Noresson et al. 1979a). Without this compensation the stroke volume would have been drastically reduced for the hypertrophied heart.     

Monoamine contents and norepinephrine turnover in brain stem nuclei of young and adult spontaneously hypertensive and Wistar-Kyoto rats

To investigate the brain stem monoamine mechanism in the development and maintenance of hypertension of spontaneously hypertensive rats (SHR), we determined monoamine contents and norepinephrine turnover in discrete brain stem nuclei which are known to relate with cardiovascular control. Specific areas and brain stem nuclei were dissected from serial frozen slices of 300 microns thickness according to the atlas of Palkovits and Jacobowitz. The dissected tissues were homogenized, centrifuged and the supernatants were injected into high performance liquid chromatography with electrochemical detection (HPLC-ECD). Norepinephrine (NE), dopamine (DA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) contents were determined. NE turnover was also determined 2 hour after alpha-methyl-p-tyrosine administration (250 mg/kg, i.p.). In 4-week old SHR, the only significant change observed was decreased NE contents in the nucleus tractus solitarii (NTS). Such decreases in NE contents of the NTS were also found in 8- and 16-week old SHR. However, there were no differences in NE turnover in the NTS between SHR and WKY. Increased NE contents were found in the A1, A5, and nucleus reticularis gigantocellularis (RG) in the later stages (8 and 16 weeks) in SHR. Furthermore, increased NE turnover was seen in the RG of SHR at 16-week old, indicating increased neuronal activity. Dopamine, 5-HT and 5-HIAA showed no consistent changes between SHR and WKY. Increased NE levels were observed in later stages after development of hypertension, suggesting the increased NE in adult SHR may represent a central adaptive change secondary to the established hypertension. Since increased NE levels were consistently found in or around the regions which are known as vasomotor centers, we assume that these increased NE might serve to maintain hypertension or to inhibit a further increase in blood pressure. In contrast, the NE contents were decreased with constant turnover in NTS of SHR aged 4, 8, and 16 weeks. Constant turnover in NE could not compensate for reduced NE in NTS and may lead to a functional reduction or reduced noradrenergic activity. This defect in intrinsic noradrenergic neurons in NTS may trigger the development of genetic hypertension in SHR. In conclusion, the present results demonstrate that NE levels of SHR in the NTS were consistently decreased compared with those of WKY in all age groups. In later stages, increased NE levels were observed in A1, A5 and RG of SHR. These results indicate that brain stem monoamine system, especially noradrenergic neurons, contributes to the development and maintenance of hypertension in SHR.     

Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats

Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SD or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats.     

阿托伐他汀影响自发性高血压大鼠血压的机制探讨

目的：探讨阿托伐他汀控制自发性高血压大鼠（SHR）高血压的机制，研究阿托伐他汀对SHR血浆内皮素-1（ET-1）和主动脉一氧化氮合酶（NOS）的影响，以及对SHR的主动脉平滑肌细胞（ASMC）凋亡和P27蛋白表达的影响。 方法： 选用8周龄SHR 12只，随机分为阿托伐他汀治疗组（ATV组, n=6）和SHR组（n=6），并以同周龄WKY（n=6）作为对照。ATV组给以阿托伐他汀（50 mg·kg-1·d-1）灌胃。10周后观察3组大鼠血压、血清总胆固醇（TC）、总甘油三酯（TG）含量变化，血浆ET-1和主动脉NOS活性的改变，以及TUNEL法检测ASMC凋亡率，测定动脉ASMC P27蛋白表达。 结果： 阿托伐他汀给药10周后，ATV组动脉收缩压显著低于SHR组［（134.17±3.60）mmHg vs （173.33±3.78）mmHg, P<0.01］；ATV组血清TC和TG浓度均显著低于SHR组（P<0.01, P<0.01）。同时，阿托伐他汀显著降低SHR血浆ET-1水平［（130.04±40.07）ng/L vs （196.74±59.69）ng/L，P<0.05］和增加SHR主动脉NOS活性［(0.189±0.040）kU/g protein vs （0.124±0.057）kU/g protein，P<0.01］；ATV组ASMC凋亡率显著高于SHR组（16.94%±3.08% vs 9.01%±2.36%, P<0.01）；ATV组ASMC P27蛋白表达阳性率显著高于WKY大鼠（33.02%±5.01% vs 24.25%±4.41%, P<0.05），而SHR组该指标明显低于WKY大鼠（16.08%±7.09% vs 24.25%±4.41%, P<0.05）。 结论： 阿托伐他汀控制SHR血压增高，其机制可能与降低SHR的血浆ET-1水平和增高主动脉NOS活性，以及增高ASMC凋亡率和P27蛋白表达阳性率有关。     

Calcium appetite, blood pressure and electrolytes in spontaneously hypertensive rats

Appetite for solutions of 0.01 M-0.1 M calcium chloride or calcium lactate were assessed using the two-bottle choice technique in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats fed calcium replete diets. SHR exhibited a marginally increased preference for calcium chloride and a significantly increased preference for calcium lactate (p less than 0.02). In SHR, but not in WKY, 28 days of calcium exposure via the preference test solutions significantly affected systolic blood pressure (p less than 0.03). The group of SHR ingesting calcium chloride had a lower mean systolic blood pressure, and that ingesting calcium lactate had a higher mean systolic blood pressure than the control group receiving no exposure to calcium in preference tests. Blood pressures of individual rats, however, were not related to cumulative milliequivalents of Ca consumed, body weight, whole blood or serum ionized Ca, K or Na concentrations, or total serum calcium. Strain differences in chemosensory sensitivity might play a role in mediating the enhanced self-selection of calcium by SHR.     

Myocardial cell growth and blood pressure development in neonatal spontaneously hypertensive rats

We evaluated the changing morphologic features of cardiac muscle cells (myocytes) and nuclei from neonatal spontaneously hypertensive rats (SHR) and their parent, normotensive strain Wistar Kyoto rats (WKY) and compared these with increasing heart weight and blood pressure development to determine if alterations in cell growth were present at this early stage of development. Femoral artery blood pressures were obtained from rats at 2 to 5-day intervals from birth to 21 days of age by using a micropipette servo-null pressure recording system. Tritiated thymidine autoradiography was used to study myocyte nuclear development, and isolated myocytes were prepared to evaluate cell-size changes by using a Coulter Counter system (Coulter Electronics, Hialeah, Florida). Heart weight and blood pressure were elevated in SHR when compared to WKY at birth. Myocytes were all mononucleated at birth in both strains and were of equal size, demonstrating that the larger heart mass in SHR was due to an increased number of cells. Heart weight relative to body weight remained greater in SHR when compared to WKY throughout the 28-day study period, but cell numbers became equal in the two strains by the 2nd week. A this time (6 to 9 days postpartum) blood pressure was also similar in both strains, but increased significantly again in SHR by 15 and 21 days of age. Cell maturation occurred earlier in SHR than in WKY as indicated by an earlier development of binucleate myocytes and there was an earlier initiation of hypertrophic myocyte growth in SHR. Increase in SHR cell size occurred at a time when blood pressures were not different, suggesting that greater cell size in SHR than in WKY was not due to differences in blood pressure. Therefore, when compared to the WKY, the SHR had three phases of altered cell growth: a first phase of accelerated hyperplastic growth during the fetal period, and a second phase (6 to 12 days of age) of earlier initiation of hypertrophic cell growth and increased myocyte size. The SHR myocyte changes in the second phase occurred while the SHR and the WKY blood pressures were not significantly different. Finally, in a third phase (at 15 days of age and over), SHR had a sustained increase in myocyte size as well as elevated blood pressure.     

Early behavioral development in the spontaneously hypertensive rat: a comparison with the Wistar-Kyoto and Sprague-Dawley strains

The spontaneously hypertensive rat (SHR) is often used as a model for childhood attention-deficit/hyperactivity disorder (ADHD). To investigate behavioral maturation in SHR, body weight, age at eye opening, and performance in several behavioral tasks in male and female SHR, Wistar-Kyoto (WKY), and Sprague-Dawley rats were compared. SHRs were slower in performing the righting reflex on PND 4 and negative geotaxis compared with WKY and Sprague-Dawley. Both SHR and WKY were delayed relative to Sprague-Dawley in eye opening and beam walking. Rotarod performance was comparable in the 3 strains. Males were faster to right themselves than females, but there were no other significant sex differences nor Sex X Strain interactions. Delayed development in SHR may be related to a maturational delay observed in children with ADHD. Research assessing early behaviors in SHR, WKY, and other strains will help determine the most appropriate model for childhood ADHD and may help predict later behavioral dysfunction.