The borderline hypertensive rat: a model for studying the mechanisms of environmentally induced hypertension

The borderline hypertensive rat (BHR) is a first-generation cross between the spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. The BHR develops frank hypertension when chronically stressed or when fed a high-sodium diet. Stress-induced hypertension can be blocked by exercise. The role of the central nervous system and kidney in hypertension development in this model is discussed.     

Behavioral hyperreactivity in the spontaneously hypertensive rat compared to its normotensive progenitor

The spontaneously hypertensive rat (SHR) is an excellent model of essential hypertensive disease. Hyperreactivity has been postulated as a contributing factor in the development of high blood pressure in the SHR and in man. In the maturing organism recurring hypertensive stress responses may promote permanent vascular changes and result in a fixed hypertension. Simple behavioral activity and emotionality rating scales were used to compare a large number of SHR with equally large groups of closely-related and distantly-related normotensive rats. As predicted, the SHR were clearly more active and emotional than their ancestral Wistar Kyoto (WKY) strain. However, the distantly-related normotensive Wistars did not differ from the SHR in either activity or emotionality. These results indicate that behavior and hypertension are not necessarily related in the rat. Nonetheless, the behavioral differences between the SHR and their closest genetic match, the WKY, suggest that arousal and blood pressure levels may be causally linked in this case of naturally occurring hypertension.     

Adult blood pressure reduction in spontaneously hypertensive rats reared by normotensive Sprague-Dawley mothers.

Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) normotensive, and Sprague-Dawley (SD) normotensive rats were either reared by their natural mothers (controls) or fostered to a mother of one of the other strains. The effects of rearing environment were assessed by measures of body weight at weaning and adult resting mean arterial blood pressure (MAP) and heart rate (HR). At weaning, SHR control rats weighed less than WKY controls which in turn weighed less than SD controls. SHR and WKY rats reared by SD mothers weighed significantly more than their respective controls, whereas SD rats reared by either SHR or WKY mothers weighed less than SD control rats. Manipulation of the maternal environment was attended by a change in adult resting MAP in only one group. SHR rats reared by SD mothers had MAPs which were significantly lower than SHRs reared by their natural mothers. No within-strain adult HR differences were observed between control and cross-fostered groups. These data indicate that the effects of cross-fostering on adult resting MAP previously reported for SHR and WKY animals are generalizable to another normotensive strain. That is, genetically hypertensive (SHR) animals exposed to a normotensive (WKY or SD) maternal environment display a reduction in adult resting MAP, whereas hypertension or an increase in adult MAP is not induced in normotensive rats (WKY or SD) as a consequence of exposure to a hypertensive maternal environment.     

Lifelong hyperarousal in the spontaneously hypertensive rat indicated by operant behavior

Instrumental conditioning techniques were used to obtain objective evidence of differences in behavioral arousal between the spontaneously hypertensive rat (SHR) and the normotensive ancestral Wistar Kyoto (WKY) strain. Subjective emotionality ratings previously indicated that the genetically hypertensive rats were more active and aggressive than their normotensive cousins. In a lengthy series of operant conditioning sessions using a small number of adult female SHR and WKY rats, hyperarousal in the SHR was confirmed by their significantly higher response outputs on either response contingent or time contingent schedules of reinforcement. Conditioned emotionality tests during this series of experiments also suggested hyperarousal and aggressiveness in the SHR, since the fear-conditioned stimulus suppressed bar-pressing in the SHR much less than in the WKY. Further experiments with young prehypertensive SHR rats provided the same evidence of hyperresponsivity in the SHR compared to the WKY strain. Furthermore, these young SHR failed to develop hypertension by the end of the study (14 weeks of age), while their nonconditioned SHR cousins had become clearly hypertensive by the same age. This suggests that factors related to the conditioning methods modified the development of high blood pressure in this animal model of essential hypertension.     

Behavioral predictors of blood pressure variation in hypertensives and normotensives

This study examined the relative impact of five behavioral factors--activity, posture, location, social involvement, and tension--on the 24-hr blood pressure (BP) variability of 21 normotensives, 18 borderline hypertensives, and 18 sustained essential hypertensives. Multiple-regression analyses indicated that within each diagnostic group, activity accounted for more variance in BP variability than any other behavioral dimension. For each behavioral dimension examined, the magnitude of the relationship with BP was generally greater for the normotensives than for both hypertensive groups. In contrast, variation due to individuals was a better predictor of BP variability for the two hypertensive groups than for the normotensive group. Number of months hypertensive and use of antihypertensive medication were related to BP variability for the sustained hypertensive group. Findings have implications for the use of ambulatory BP monitors and interpretation of resulting data.     

Auditory startle in normotensive and hypertensive rats

In the present experiment auditory startle was examined in male and female rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) strains and borderline hypertensive rats (BHR) derived from cross-breeding SHR females with WKY males. The magnitude of auditory startle declined over trials and was significantly higher in WKYs than in both SHRs and BHRs which did not differ from each other. These data add to an increasing body of literature concerning behavioral differences between hypertensive and normotensive rats and are discussed as they relate to the possible strain differences in either behavioral reactivity or tonic fear.     

Effects of hypertension on attention, memory, and executive function in older adults.

Hypertension is associated with impairments in cognitive function in older adults, but the nature and extent of these deficits are unclear. Brief cognitive measures lack sensitivity, whereas comprehensive assessments produce numerous variables that are difficult to interpret. The authors performed a principal-components analysis using a computerized cognitive assessment battery and neuropsychological measures of executive function in 506 hypertensive and normotensive older participants. Composite factor scores were used to reanalyze data from 223 untreated participants without vascular complications. The hypertensive group had deficits in Speed of Cognition, Episodic and Working Memory, and Executive Function but not Continuity of Attention. Using composite scores simplified data interpretation and suggested differential effects of hypertension on cognitive performance not clearly evident in individual test results.     

Independence of blood pressure and locomotor hyperactivity in normotensive and genetically hypertensive rat

The spontaneously hypertensive rat (SHR) exhibits locomotor hyperactivity in comparison to its normotensive progenitor Wistar-Kyoto (WKY) strain. We asked whether the hyperactive behavior was a direct consequence of elevated blood pressure in the hypertensive rat. Three experimental protocols were used to chronically alter blood pressure. In the first protocol, a group of adult SHRs was given hydralazine (20 mg/kg/day) in their drinking water to lower blood pressure. These animals exhibited a significant decrease in blood pressure, but no change in locomotor activity. In the second protocol, young SHRs (4 weeks of age) were treated with the same dosage of hydralazine until 16 weeks of age. Blood pressure was significantly decreased in these animals with no change in locomotor activity. In the third protocol, normotensive WKY and Sprague-Dawley (SD) rats were made hypertensive with unilateral renal clips. The resulting increase in blood pressure in these animals did not alter locomotor activity. These results suggest that locomotor hyperactivity is an inherent property of the SHR and is independent of blood pressure.     

Slowing of memory-search performance in men with mild hypertension

Previous reports have associated hypertension with a slowing of cognitive performance, although the component processes involved have not been identified. Our report compares the performance of 24 men with mild hypertension and 28 age-matched normotensive men on a test of short-term memory search in which the duration of component processes could be estimated. The results indicated that the rate of search through short-term memory was slower for the hypertensive than for the normotensives, whereas the duration of encoding and response processes was equivalent for the two groups. This hypertension-related slowing of memory comparison was independent of participants' error rates and education levels.     

Stress ulcer and open-field behavior of spontaneously hypertensive,normotensive, and Wistar rats

Spontaneously hypertensive rats (SHRs) and the normotensive Wistar/Kyoto (WKY) rat were observed, along with Wistar rats (which represent the parent strain), on various open-field behaviors. All three strains were subsequently exposed to the activity-stress (A-S) ulcerogenic procedure. SHR and Wistar rats were very active in most open-field measures as compared with WKY rats, but only SHRs were active during the A-S treatment. WKY rats were very ulcer prone and had significantly more ulcers than SHRs, which in turn had more ulcers than Wistar rats. It was anticipated that Wistar rats would resemble the WKY rats, but in most measures the Wistars resembled the SHRs. The study suggests that although WKY rats function as an appropriate control for hypertension studies, these rats may be inappropriate as controls for other physiological and behavioral studies.     

Effects of a high salt diet on blood pressure responses to acoustic stimuli in borderline hypertensive rats (BHR)

The borderline hypertensive rat (BHR) responds to environmental and dietary stressors with elevated blood pressure. The first two months of a high salt diet appear to be the time of greatest sensitivity to salt effects on the blood pressure of BHR. The current study was conducted to examine whether exposure to salt diets varying in duration for up to two months differentially affects baseline blood pressures (systolic, SBP, and diastolic, DBP) and blood pressure responses to novel acoustic stimuli in BHR and normotensive Wistar-Kyoto (WKY) rats. Male BHR and WKY were fed a control (1%) salt diet or a high (8%) salt diet for 1, 1.5, 2.5, or 8.5 weeks. SBP and DBP responses to an acoustic stimulus (85 dB, 3 kHz) were measured upon completion of the diets at 12 weeks of age. Ten acoustic trials (one stimulus/minute) were presented and blood pressure responses were recorded in 2-second blocks spanning the 10 seconds prior to and following stimulus presentation. BHR had higher resting SBP and DBP than WKY, and 8.5 weeks of 8 percent salt increased SBP markedly in BHR. SBP and DBP labilities in the initial trial were greater in BHR than WKY with high salt diet durations of 2.5 and 8.5 weeks producing greater lability in later trials. Few differences were noted in pressor responses, but BHR had more dramatic depressor responses than WKY in early trials, and BHR pressures had a more dramatic return to baseline. It appears that genetic history and salt diet can affect blood pressure lability and recovery in response to novel stimuli in genetically susceptible animals.     

An exploratory study on the development of beliefs about symptoms as signals of arterial hypertension

An exploratory study on the development of beliefs about symptoms as signals of arterial hypertension. In spite of hypertension is known as an asymptomatic health problem, most of the people with such a diagnosis are convinced of experiencing very specific symptoms associated to specific changes in blood pressure (BP). In addition, such beliefs may affect treatment adherence. Previous studies have shown that hypertensive patients use the information they considered right about BP symptoms to regulate the type of decisions they follow in adhering to treatment. The aim of this study is to explore specific variables related with the formation of beliefs about symptoms in a sample of 171 hypertensive patients. Results show that 81,3% of the patients perceived specific symptoms related to changes in hypertension as well as that variables related with the development of these beliefs were mostly: (1) the presence of symptoms during the diagnosis process, (2) the occurrence of hypertensive crisis, and (3) the information provided by others concerning the relationships between symptoms and BP changes. The importance of paying attention to the beliefs of specific symptoms as well as to the circumstances related with the formation process of such beliefs is discussed.     

Emotional inhibition in essential hypertension: obstacle to communication during medical visits?

A substantial literature on the "hypertensive personality" links essential hypertension (EH) with the suppression of negative emotions, implying that suppression may elevate blood pressure. Yet affective inhibition might also impair communication with health care providers and exacerbate EH by limiting therapeutic collaboration. We studied 542 patient-physician interviews from a national sample to see if patients with EH (n = 203) were less likely to exhibit negative emotions than normotensive patients (n = 339) as rated by their physicians and independent observers. EH patients did not differ from others on self-rated emotional or physical health. However, physicians were less accurate in characterizing the emotional states of EH patients than those of normotensive patients, and they rated EH patients as exhibiting fewer signs of distress during the visit. Independent observers also judged the EH patients as less distressed than normotensives, thereby validating the physicians' appraisals. Content analysis disclosed that physicians paid less attention to psychosocial concerns and concentrated on biomedical matters to a greater degree with hypertensive patients than with their normotensive patients. EH patients, particularly those experiencing emotional distress, appear to have patterns of self-presentation that could present an obstacle to effective communication with their physicians, and this difficulty may be amplified by physicians' disinclination to probe for emotional difficulty.     

Behavior analysis and the search for the origins of hypertension.

Hypertension is a disorder of sodium regulation that develops over time in a context of the interactions of the individual with the environment. Experimental hypertension can be induced in laboratory animals and normotensive humans via increases in sodium intake under conditions of aversive behavioral control. Readiness for avoidance contingencies includes a breathing pattern characterized by subnormal rate and normal tidal volume. Studies with humans have shown that this inhibitory breathing pattern is associated with increased plasma acidity, increased renal sodium reabsorption, increased secretion of digitalis-like hormones that inhibit sodium-pump activity, and increased vasoconstriction and blood pressure. Behavioral research is needed that defines the necessary and sufficient conditions for inhibitory breathing and its role in the development of hypertension.     

Inbreeding of Wistar-Kyoto rat strain with hyperactivity but without hypertension

A genetic inbreeding program using Wistar-Kyoto rat strains as progenitors was used to combine the hyperactivity trait of the spontaneously hypertensive rat (SHR) with the normotensive trait of the WKY genetic control strain. From an SHR X WKY cross we produced a gene-assorting F2 population from which selected brother-sister matings were carried out through seven successive inbred populations. This program produced a new strain of hyperactive rats with normotensive mean systolic blood pressure levels, and we have designated the new strain as the Wistar-Kyoto hyperactive (WK/HA) rat. Another behavioral characteristic of the SHR rat, poor habituation in a nonreinforcing novel environment, did not appear as a characteristic trait of the new strain of WK/HA rats, suggesting a separate underlying genetic basis for the two traits that had been apparently fortuitously fixed in the SHR genotype as a result of intensive inbreeding of that strain. The new WK/HA strain, together with the WKY control strain, is considered as more suitable for subjects in studying hyperactivity in rats than the original SHR strain with its concomitant hypertension and poor habituation traits.     

Differences in personality between sustained hypertension,isolated clinic hypertension and normotension

The aim of this study was to determine whether there are differences in personality between hypertension and normotension. Forty‐two male patients with essential hypertension were divided into two groups after self‐assessment of blood pressure, 18 with sustained hypertension and 24 with isolated clinic (white coat) hypertension, and were compared with 25 men with normotension on Spielberger's State‐Trait Anxiety Inventory and the Jenkins Activity Survey. In line with hypotheses, the sustained hypertensive group showed higher levels of trait anxiety, Type A behaviour pattern, and hard‐driving behaviours/competitiveness than the normotensive group, whereas isolated clinic hypertensives occupied an intermediate position between those two groups. Results provide support to the hypothesised relationship between personality and hypertension and stress the need of distinguishing sustained hypertension from isolated clinic hypertension. Copyright © 2006 John Wiley & Sons, Ltd.     

Open-field behavior of one-clip, two-kidney hypertensive rats: the influence of pre-handling

The relation between the development of hypertension and changes in behavior was investigated. Hypertension was induced by unilateral application of a 0.20-mm clip around the renal artery. At 4 weeks, but not at 1 week, after the operation an increase in ambulation was found. Blood pressure was significantly increased at 1 (28 mm Hg) and 4 weeks (78 mm Hg) after the operation. In a second experiment, renal hypertensive rats and controls were either regularly handled (i.e., subjected to indirect tail-cuff blood pressure measurements) or left undisturbed. At 4 weeks after clip implantation, only in the nonhandled rats with renal hypertension, an increase in open-field ambulation was found. Blood pressure was markedly increased in both handled and nonhandled renal hypertensive rats.     

Open-field behavior in two models of genetic hypertension and the behavioral effects of salt excess

In order to assess the relationship of behavior to blood pressure and salt intake, open-field behavior was studied in 123 rats of the spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), Sprague-Dawley (SD), and Dahl resistant (DR) and sensitive (DS) strains. DS rats become hypertensive upon exposure to either high dietary salt or psychogenic stress, while DR rats remain normotensive. A circular photobeam open field was used under full room illumination. Three 5-min trials were given on consecutive days. Rats were tested with or without 5 days of an 8% NaCl diet. We found that DS rats were less active than DR rats, regardless of diet. In contrast, SHR rats were more active than WKY rats. However, DS and SHR rats were equally active. Thus, behavioral differences between these two models of hypertension are expressed by the normotensive control strains. The relative ranking of activity levels between strains was DR = SD greater than SHR = DS greater than WKY. High-salt-enhanced intertrial habituation, defined as the decrease in activity across trials (DS, 100%; SD, 82%; SHR, 90%; WKY, 1350%; but DR, -50%) as well as intratrial habituation, defined as the decrease from the first to the second half of the trial (14%, all subjects). Defecation was increased with high salt (DS, 975%; SD, 59%; SHR, 267%; WKY, 89%; but DR, 40%). These effects of high salt may reflect an increase in an emotionality factor. DR rats were largely resistant to the behavioral effects of salt. Total activity was positively correlated with blood pressure in hypertensive rats, r(42) = 0.33, p less than .01, but negatively correlated in normotensive rats, r(81) = -0.34, p less than .01. The proportion of total activity occurring in the first half of the trial for the initial test day was correlated with blood pressure in normotensive rats r(81) = 0.44, p less than .01. Dietary salt excess has behavioral as well as cardiovascular consequences.     

A longitudinal study of pain sensitivity and blood pressure in adolescent boys: results from a 5-year follow-up.

A growing literature has observed a significant reduction in pain sensitivity among hypertensive animals and humans. It is uncertain whether a reduced sensitivity to pain can be observed in nonnotensive individuals who go on to develop high blood pressure. Blood pressure (BP) was reassessed in one hundred fifteen 19-year-old boys initially tested at age 14, when they were also presented with a pain stimulus (mechanical finger pressure). Hierarchical regression analyses indicated that information regarding pain tolerance improved prediction of changes in systolic and diastolic blood pressure beyond that afforded by differences in BP at age 14, parental history of hypertension, and body mass index. These analyses suggest that pain sensitivity may be associated with physiological processes involved in the development of sustained high blood pressure.     

Independent effects of geometry and landmark in a spontaneous reorientation task: a study of two species of fish

While disoriented humans and animals use both landmarks and environmental geometry to guide their navigation, it is not clear what kinds of cognitive mechanisms underlie these behaviors. Because traditional tests of trained navigation behavior in environments containing both landmarks and geometric information may cloud our insight into the nature of these processes, the present study tested the spontaneous use of landmarks and environmental shape by two species of fish-Redtail Splitfins (Xenotoca eiseni) and Zebrafish (Danio rerio). The results suggest that while geometry is spontaneously used by both species and both sexes to compute relative position or direction, the spontaneous use of landmarks is limited to direct beaconing and complicated by attraction to features and variability across species and sex. These findings support the view that while multiple cues may ultimately guide behavior, the computation of orientation and relative positions is specified by geometric input and is independent from other navigation processes such as beaconing.