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Biomedical subjects

E D Hendley

Publications and source records attributed to E D Hendley.

14 recordsLinked to original sources
PubMed1992

Regional differences in brain norepinephrine and dopamine uptake kinetics in inbred rat strains with hypertension and/or hyperactivity.

High-affinity uptake of norepinephrine (NE) and dopamine (DA) were determined in synaptosomes of brain regions from four genetically related inbred rat strains, all derived from the Wistar-Kyoto rat: SHR, WKY, WKHA and WKHT strains. SHRs express hypertension and hyperactivity, WKHAs express hyperactivity alone, WKHTs express hypertension alone, and WKYs are neither hypertensive nor hyperactive. Significant increases in NE uptake, primarily in Vmax, in cerebral cortical areas and the cerebellum, were associated with the hypertensive trait. Significant increases in DA uptake Vmax in the frontal cortex were associated with the inheritance of hyperactivity among these strains. A limited study in SHRs indicated that DA uptake in the frontal cortex increased with age, and that males did not differ from females. No changes in DA uptake in the neostriatum were found with respect to either strain, or age or sex. These findings revealed changes in brain catecholamine neuronal function that are of relevance to both hypertension and hyperactivity. This was made possible by the availability of WKHA and WKHT, in addition to WKYs, as appropriate controls for the SHR.

Aging↗
PubMed1992

Interstrain aggression in hypertensive and/or hyperactive rats: SHR, WKY, WKHA, WKHT.

Four inbred rat strains, all derived from Wistar-Kyoto (WKY) rats, express hypertension and hyperactivity in all combinations: SHRs have both traits, WKYs have neither, WKHAs are hyperactive/normotensive, and WKHTs are hypertensive/normoactive. Rats of the four strains were tested for aggression, at one time only, by pairing subjects of same sex, same age, but different strain, in a novel arena, i.e., on neutral ground, for three consecutive, 5-min observation periods. Total aggression scores were highest in females, highest in the first 5-min period, and lower at 7-9 months than at younger ages. Allogrooming was more frequently observed than other types of aggression, such as attacks, mounts, aggressive postures, and blocks. Allogrooming scores were significantly elevated in the hypertensive strains, especially WKHT, and very low in the hyperactive strains, especially WKHA. The other forms of aggression were significantly higher in females with hyperactivity. It was concluded that interstrain aggression, as seen in SHRs and WKYs, is differentially expressed by two new strains genetically derived from them. Furthermore, no one strain among these four expresses all components of the behavioral responses seen in this form of aggression.

Aggression↗
PubMed1992

Behavior of hypertensive and hyperactive rat strains: hyperactivity is not unitarily determined.

The spontaneously hypertensive rat (SHR) is behaviorally hyperactive relative to the Wistar-Kyoto rat (WKY). By breeding SHR with WKY, followed by inbreeding, two new strains have been developed in which hypertension seems to be separated from hyperactivity to novel stimuli: the WKHT and the WKHA strains. The main purpose of the present study was to determine which behavioral characteristics of SHR have been dissociated from the hypertensive trait in the WKHA strain. Male SHR, WKY, WKHT, and WKHA were subjected to three protocols: 1) Two forced-exploration tests, where the results showed that both the SHR and the WKHA rats were hyperactive. 2) A free-exploration open field, where the SHR was more active than the other strains, showing shorter latencies to leave the home cage, spending more time in the field, ambulating and rearing more. Furthermore, the WKHT behavior was more similar to the SHR behavior than the WKHA behavior. 3) A two-component schedule of reinforcement, where one component (fixed-interval 2 min) was signaled by houselight on and the other (extinction, EXT) by houselight off. In this test, the SHR behavior was markedly different from that of the three other strains: the fixed-interval scallop, the accelerated responding towards the end of the interval, was steeper in SHR than in the other groups. The SHR emitted more responses during the extinction component of the schedule. The SHR hyperactivity was dependent upon the reinforcement value of the water deliveries and was increased even further by sensory-reinforcing respones feedback lights. Thus, the hyperactivity of the WKHA strain seems to be less pervasive than that of the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Two new inbred rat strains derived from SHR: WKHA, hyperactive, and WKHT, hypertensive, rats.

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.

Activity Cycles↗
PubMed1991

Hypertrophy of stellate ganglion cells in hypertensive, but not hyperactive, rats.

The dendritic complexity of peripheral autonomic neurons is positively matched with the size of the target they innervate, apparently by trophic interactions with the target (D. Purves, W. D. Snider, and J. T. Voyvodic. Nature Lond. 336: 123-128, 1988). We have asked whether the vascular hypertrophy associated with hypertension is accompanied by dendritic hypertrophy of sympathetic ganglion cells. To do this, we examined the morphology of stellate ganglion cells in the spontaneously hypertensive rat (SHR), its normotensive control Wistar-Kyoto rat (WKY), and two new strains derived from the SHR that independently express the hypertensive phenotype of the SHR (WKHT) and the behavioral hyperactivity present in the SHR (WKHA). Cells were examined by intracellular staining with horseradish peroxidase in in vitro preparations of the ganglia. Carotid arterial wall size was also examined. Significant hypertrophy of both the carotid arterial wall and stellate ganglion cell dendrites was observed in the two hypertensive strains (SHR and WKHT) but not in either of the normotensive strains (WKY and WKHA). This increased total dendritic length of stellate ganglion cells associated with hypertension provides a greater target area for preganglionic innervation that may result in hyperinnervation of these cells.

Animals↗
PubMed1991

Two new Wistar-Kyoto rat strains in which hypertension and hyperactivity are expressed separately.

Two inbred strains have been developed from a cross between SHR and WKY. WK-HTs are hypertensive but not hyperactive, and WK-HAs are hyperactive but normotensive. Together with SHR (that express both traits) and WKY (expressing neither trait) we used four strains to follow correlations of biological changes with the expression of hyperactivity or hypertension. We show that the well known sympathetic hyperreactivity of SHRs to acute stress is associated with the hyperactivity trait and not the hypertension among the four strains. Similarly, the well known ventricular hypertrophy in SHRs is more prominent among the hyperactive strains than the hypertensives. Examination of regional brain amine levels revealed an imbalance in forebrain serotonin transmission in the hyperactive strains, and no significant correlations with hypertension. On the other hand, neuropeptides in brainstem and spinal cord revealed a decrease, in hypertension, in neuropeptide Y and PNMT content of terminals of C1 fibers that innervate the spinal cord sympathetic outflow. Also, the two hypertensive strains showed increased TRH-and proctolin-like immunoreactivity in fibers that innervate the C1 cells in the rostral ventrolateral medulla. These findings illustrate the unique advantage provided by WK-HA and WK-HT strains as additional controls for SHRs in studying hypertension and hyperactivity.

Adrenal Medulla↗
PubMed1990

Association between cardiovascular reactivity to stress and hypertension or behavior.

The spontaneously hypertensive rat (SHR) exhibits increased cardiovascular reactivity (CVR) to environmental stress and behavioral hyperactivity relative to the Wistar-Kyoto rat (WKY). This study sought to determine whether enhanced CVR to stress in the SHR is related to hypertension or to behavioral hyperactivity. By breeding SHR with WKY, followed by inbreeding, E. D. Hendley has developed two strains in which the hypertensive trait seems to be separated from the hyperactivity trait: the Wistar-Kyoto hypertensive (WK-HT) and the Wistar-Kyoto hyperactive (WK-HA) strains. Male SHR, WKY, WK-HT, and WK-HA rats were implanted with intravascular catheters and Doppler flow-velocity probes to record arterial pressure, heart rate (HR), and changes in regional vascular resistances. Five days after surgery, the rats were subjected to air-jet stress and pharmacological interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced pressor, renal, and mesenteric responses to stress, and higher HRs under all conditions, even after autonomic blockade. Both hypertension and hyperactivity were associated with reduced baroreceptor sensitivity. These data indicate that CVR to stress is related to behavioral traits.

Adrenergic beta-Antagonists↗
PubMed1989

Extracellular ATP stimulates norepinephrine uptake in PC12 cells.

This study examined the effects of extracellular ATP on norepinephrine (NE) uptake, using PC12 cells as a model of noradrenergic neurons. Previous experiments with synaptosomes led to the hypothesis that extracellular ATP can regulate NE uptake via an ecto-protein kinase. In the present study, we examined the high-affinity uptake of NE (referred to as uptake 1) in PC12 cells in the presence of varying concentrations of extracellular ATP. In the presence of Ca2+, low concentrations of ATP (0.1 microM) increased uptake 1 by approximately 36%. This increase could be mimicked by adenosine-5'-O-(3-thiotriphosphate) tetralithium salt (ATP gamma S), an analogue of ATP which can be utilized by protein kinases, and not by 5'-adenylylimidodiphosphate tetralithium salt, a nonhydrolyzable analogue of ATP, GTP, ADP, and adenosine also had no effect on uptake 1. Preincubation of the cells with NE and ATP gamma S, followed by washing and assaying NE uptake 30 min later, resulted in a persistent increase in uptake 1. Similar pretreatment with ATP did not show this increase; however, simultaneous pretreatment with ATP and ATP gamma S blocked the activation produced by ATP gamma S alone. Kinetic analysis showed that ATP gamma S pretreatment produces an increase in the Vmax of uptake 1 without altering the apparent Km for NE. These results support the hypothesis that extracellular ATP can regulate NE uptake via an ecto-protein kinase.

Adenosine Triphosphate↗
PubMed1988

Brain monoamines and metabolites in hypertensive and hyperactive rat strains.

Monoamines and metabolites were measured by HPLC-EC in brain regions of four Wistar-Kyoto derived rat strains, in whom the traits of genetic hypertension or hyperactive behavior were expressed together (SHR), separately (WK-HT and WK-HA strains, respectively), or not at all (WKY). These genetically related inbred strains were used to allow more discrete correlations between neurochemical changes and the hypertensive and/or hyperactive state, than was hitherto possible using SHR and WKY metabolite levels were present in the six brain regions examined, however, no correlations with hypertension were observed. Limited correlations were seen between hyperactivity and forebrain serotonergic systems. These findings demonstrate that neurochemical differences between SHR and WKY may be erroneously attributed to the hypertension and/or hyperactivity of the SHR, unless additional genetic control strains, such as WK-HT and WK-HA rats are utilized.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Acute stress and the brain norepinephrine uptake mechanism in the rat.

The kinetic constants for norepinephrine uptake in cerebral cortical homogenates were determined in vitro immediately following an acute stress consisting of either forced immobilization, cold-wet exposure, combined cold-plus-restraint, swim stress, or electric footshock in the rat. The kinetic constants, apparent Km and Vmax, for uptake of 3H-l-norepinephrine were significantly increased only following 10 min swim at 22 degrees or following 5 min electric footshock. When severe hypothermia accompanied the stress, the findings suggested that a profound reduction in body temperature was associated with depressed responsiveness of brain noradrenergic mechanisms to stress including decreased uptake kinetic constants. In a series in which the duration of electric footshock was varied from 2 to 30 min, it was noted that the NE uptake kinetic constants were increased at 5 min, but were similar to paired controls at 2, 10 and 30 min following the onset of footshock. It was concluded that various acute stresses did not elicit a generalized response of the cortical NE uptake mechanism to stress in the rat. Furthermore, when uptake kinetic constants did change with stress, the values were often within the range of normal values seen in the rat.

Animals↗
PubMed1976

Electroconvulsive shock and norepinephrine uptake kinetics in the rat brain.

The kinetic constants, apparent Km and Vmax, for the uptake of 3H-1-norepinephrine in cerebral cortical homogenates of the rat brain were not altered 5 min after a single electroconvulsive shock (ECS). However, one day after the last of a series of 14 ECS the apparent Km and Vmax were significantly increased above sham-shock controls, and ECS rats lost weight. Three days after the last ECS apparent Km and Vmax were significantly decreased, while the rate of weight gain tripled in the ECS rats. One week after the last ECS the kinetic constants and rate of weight gain were no different from sham-shock controls. These data are indicative of the strong compensatory mechanisms in the normal rat to the alterations induced by ECS.

Animals↗