Biomedical subjects

J E Lawler

Publications and source records attributed to J E Lawler.

At least 19 recordsLinked to original sources

PubMed1999

Sympathetic control of BP and BP variability in borderline hypertensive rats on high- vs. low-salt diet.

This experiment tested the effect of a high-salt diet on the interaction between arterial blood pressure (BP) and sympathetic nerve activity (SNA) at rest and during a controlled behavioral stress at an early stage in the development of hypertension in borderline hypertensive rats (BHR). Ten rats were maintained on a high-salt diet (8% NaCl) while 14 were fed a low-salt diet (0.8% NaCl) for 8 wk. They were trained in a Pavlovian paradigm by following a conditional stimulus tone (CS+) with a 0.5-s shock. SNA and BP were measured by implanted electrodes around the left renal nerve and a catheter in the femoral artery, respectively. There were no detectable between-group differences in BP or in BP variability in the resting animal at the end of the 8-wk dietary treatment. Moreover, there were no significant between-group differences in the changes in SNA evoked by the CS+ tone. Conversely, the amplitude of the initial conditional increase in BP was significantly (P < 0.05) larger in the high-salt (6 +/- 0.6 mmHg; mean +/- SEM) compared with the low-salt (4 +/- 0.4 mmHg) group. In addition, the BP excursion (peak/trough) during CS+ was larger in the high (18.2 +/- 6.1 mmHg)- vs. low-salt (5.8 +/- 0.4 mmHg) diet-fed subjects. The ratio of the average percent change in mean BP to the average percent change in SNA at the beginning of CS+ was 0.029 +/- 0.004 for the low-salt group and 0.041 +/- 0.006 for the high-salt group. We find that, before the development of overt hypertension, the enhanced conditional BP response in the high-salt BHR appears to reside at the interface between changes in SNA and the effector response and not within the central nervous system. These observations help explain the increasing BP variability typically observed with the development of hypertension in humans.

Animals↗

PubMed1997

Sympathetic nervous activity and arterial pressure responses during rest and acute behavioral stress in SHR versus WKY rats.

The object of this experiment is to compare changes in renal sympathetic nerve activity (SNA), mean arterial blood pressure (MAP) and heart rate (HR) during rest and behavioral stress in 12-14 week old spontaneously hypertensive rats (SHR; N = 12) and normotensive Wistar-Kyoto (WKY; N = 12) controls. Animals were behaviorally trained by following a 15 s auditory conditional stimulus (CS+) with a 1/2 s tail shock. Resting MAP was higher (p < 0.001) in SHR (154 +/- 3 mmHg, mean +/- SEM) compared to WKY (116 +/- 3 mmHg); conversely, there was no difference in the average resting HR. The pattern of the SNA and MAP changes during the CS+ was similar across groups, but the amplitude was larger in the SHR. The CS+ stress stimulus evoked an initial transient MAP increase averaging 14 +/- 2 mmHg in the SHR compared to 4 +/- 1 mmHg in the WKY. This pressor response was preceded by a sudden burst of SNA averaging 177 +/- 22% over baseline in SHR versus 105 +/- 13% for the WKY. HR decreased in SHR only during the second component of the CS+ trial despite the large increase in SNA. We conclude that (1) SHR have higher reactivity than WKY to stress in SNA and MAP; (2) both SHR and WKY have greater SNA and MAP responses to CS+ than CS-(i.e., the discriminative paradigm was effective); (3) control of sympathetic and parasympathetic nervous activity during sustained stress differs remarkably in hypertensive and normotensive subjects; and (4) SHR blood pressure effector mechanisms may have a higher responsiveness to sympathetic nervous activity as compared to WKY.

Animals↗

PubMed1996

Norepinephrine levels in discrete brain nuclei in borderline hypertensive rats exposed to compound stressors.

The borderline hypertensive rat (BHR) appears to be an appropriate model for investigating the role of the environment in producing hypertension. Previous studies have demonstrated that the BHR shows chronic blood pressure elevations to both stress and high salt intake. Other studies suggest that interactions between the brain and kidney play an important role in initiating this hypertension. The central noradrenergic system has been implicated in these effects, especially in the hypothalamus. Because exercise has been found to attenuate stress-induced hypertension in the BHR, the current study sought to examine the impact of stressors paired with exercise (salt intake or stress) with those combining stress and high salt. Male BHR were exposed to either control, salt plus stress, salt plus exercise, or stress plus exercise conditions for either 2 or 6 months, beginning at 2 months of age. Following sacrifice, brain nuclei in the brain stem and hypothalamus were removed using the Palkovits micropunch technique. Punches were analyzed for NE content via liquid chromatography with electrochemical detection. Compared with the control condition, chronic salt plus stress led to reductions in NE content, especially in the hypothalamus. Compared with salt plus stress, the exercise conditions were associated with elevated NE levels, especially in the early phases of exposure to the treatment. The possible role of exercise training in preventing a central nervous system trigger from inducing hypertension in the BHR is discussed.

Animals↗

PubMed1994

Changes in creatine kinase expression induced by exercise in borderline hypertensive rat hearts.

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.

Animals↗

PubMed1993

Effects of salt intake on blood pressure and heart rate responses to footshock stress in SHR, BHR, and WKY rats.

The SHR shows chronic elevations in blood pressure in response to stress or a high salt diet, at least in some studies. Stress and salt have also been combined in studies in the SHR. Tonic levels of blood pressure are not clearly elevated by superimposing acute stress on top of a chronic high salt diet. The BHR is a new model with lower resting blood pressure and marked sensitivity to environmental stressors such as stress and dietary salt intake. In the present study, SHR, BHR, or WKY were placed on a normal or high salt (8% in chow) diet. During the 8th week of the appropriate diet, blood pressure and heart rate were monitored during rest and footshock stress. Salt elevated the resting blood pressure in all three strains, but only marginally in the WKY. Stress did not further elevate the effect seen with salt, although it had a differential effect on heart rate in the three strains. In SHR, the salt group had a higher heart rate, although in BHR it was no different, and in WKY it was lower, than that seen in same-strain normal diet groups. The results are discussed in terms of the ability of the combination of stress and chronic high salt intake to alter baroreflex function in SHR, although only marginally affecting it in BHR. WKY, on the other hand, do not show evidence of altered baroreflex function when an acute stressor is superimposed on a high-salt diet.

Animals↗

PubMed1993

Predictability of foot shock differentially affects the phasic blood pressure of SHR, BHR, and WKY rats.

Because animals prefer predictable over unpredictable shock, it was hypothesized that rats receiving unpredictable foot shock would show greater phasic blood pressure responses. Furthermore, because some studies utilizing human subjects suggest that blood pressure responses to stress are greater in those with a positive family history of hypertension, the current study examined the phasic blood pressure response to alterations in foot shock predictability in rats with either zero, one, or two hypertensive parents. Predictability was manipulated by altering the percentage of trials during which foot shock was associated with a tone, while at the same time keeping the total number of foot shocks equal in all groups. During the first few trials, the most unpredictable foot shock was associated with higher blood pressure, a trend that was significant for the borderline hypertensive rat (BHR) and marginal for the spontaneously hypertensive rat (SHR). It was also noted that, over the 28 foot-shock trials comprising the stress session, habituation of the blood pressure response was obtained for the most unpredictable shock group. Again, this occurred in those rats with a genetic history of hypertension (SHR and BHR). The results are discussed in relation to studies of stress and blood pressure reactivity in humans with a positive family history of hypertension.

Animals↗

PubMed1993

A chronic high-salt diet fails to enhance blood pressure reactivity to a tone associated with footshock in SHR, BHR, and WKY rats.

Both the human and animal literatures suggest that reactivity to stress is enhanced in the presence of a positive family history of hypertension. There is also some suggestive evidence, though not as strong, that a high-salt diet will enhance reactivity to stress, at least in a subpopulation of individuals. In the present study, rats with zero (Wistar-Kyoto, or WKY), one (borderline hypertensive, or BHR), or two (spontaneously hypertensive, or SHR) hypertensive parents were placed on a normal or high (8% in chow)-salt diet for 8 weeks starting at 8 weeks of age. After 6 weeks on the appropriate diet, rats were stressed daily for 5 days. Each session consisted of 28 foot shock trials preceded by a tone. On the following week, animals were instrumented with femoral artery catheters. After a 2-day recovery period, they were again subjected to the experimental paradigm, during which blood pressure was continuously monitored. Differences were found with respect to blood pressure reactivity and family history: SHR were the most reactive to the tone associated with foot shock. However, no effects of salt on reactivity were observed, despite an effect of this manipulation on basal blood pressure. The effect of foot shock itself was also studied, and revealed that BHR showed a blood pressure reactivity response intermediate between SHR and WKY. Once again, no effects of the salt manipulation were seen. In conclusion, while the data support a relationship between family history of hypertension and reactivity to stress, they do not support a relationship between salt intake and reactivity to stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The borderline hypertensive rat (BHR) as a model for environmentally-induced hypertension: a review and update.

In recent years, the burgeoning disciplines of health psychology and behavioral medicine have renewed interest in the important role that environmental factors can play in the disease process. Nowhere is this concern more well-founded than in the area of cardiovascular disorders, particularly hypertension. Epidemiologists and clinicians have long suspected that stressful life events can be a sufficient trigger for the expression of hypertension in some individuals. To understand better the ways in which these variables interact in the disease process, researchers have tried, with limited success, to produce experimental hypertension in animals by exposing them to stressful environmental paradigms. Additionally, recent investigations using the borderline hypertensive rat (BHR) have demonstrated the important role genetic factors can play in mediating both the behavioral and cardiovascular responses to environmental stressors. The current paper will review these attempts and discuss recent data from experiments using a relatively new animal model that appears to be especially appropriate for the study of environmental-genetic factors in the elaboration of essential hypertension. We will also discuss potential mechanisms by which environmental stress influences arterial pressure and suggest avenues for further inquiry into the stress-disease relationship.

Animals↗

PubMed1991

Family history of hypertension, gender, and cardiovascular responsivity during stress.

The relationships of family history of hypertension and gender to cardiovascular responses to stress were investigated in this research. One hundred twenty-three subjects were monitored while they rested and performed two tasks, reaction time and Ravens progressive matrices. Positive-family history males exhibited higher levels of systolic blood pressure than the negative male group and higher levels of rate pressure product than the positive-family history female group. Positive-family history males also had heart rate levels as high as the females. Female subjects did not differ from each other based on family history. In addition, subjects were grouped by gender and by high- or low-heart rate reactivity. The results suggest that heart rate reactivity has equally broad effects on cardiovascular function for males and females; for males, this reactivity during rests and tasks also tends to be associated with family history of hypertension.

Adolescent↗

PubMed1991

Baroreflex function in chronically stressed borderline hypertensive rats.

A number of previous studies have demonstrated that some aspect of baroreflex function is altered as hypertension develops. However, no studies have determined whether a chronic stressor can alter baroreflex function in the resting state. In the present study, male borderline hypertensive rats (BHR) were divided into three groups: control, stressed daily for 5 weeks, and stressed daily for 11 weeks. At the appropriate time, 7 different dosages of angiotensin II (AII) were given intravenously as a bolus injection. Heart rate (interbeat interval, or IBI) and mean arterial pressure were tracked for 90 subsequent beats. For each group, intercorrelations between pressure and IBI were obtained. In addition, overall means of pressure and IBI for each dosage were computed for each group and plotted. Higher dosages of AII were required to produce a significant correlation between pressure and IBI in the 5-week group compared to control. In the 11-week group, only the highest dosage yielded a significant correlation between pressure and IBI. When data were expressed in terms of the highest pressure and its corresponding IBI for each group, the 5-week-stress group had a shift in set point compared to control. The 11-week group showed a shift in set point and a reduction in gain compared to control animals. The similarity between these findings and those for other models of hypertension is discussed, with special emphasis on the potential role of the central nervous system.

Angiotensin II↗

PubMed1989

Norepinephrine content of discrete brain nuclei in acutely and chronically stressed borderline hypertensive rats.

Forty-three male borderline hypertensive rats were subjected to either 3 days, or 4, 10, or 16 weeks of daily stress. An additional 43 animals served as unstressed, age-matched controls. At the end of study, animals were sacrificed, brains were removed, and cardiovascularly-important nuclei in the brainstem and hypothalamus were removed by micropunch. Assays revealed that norepinephrine (NE) levels were initially elevated in the brainstem in animals stressed for 3 days. As stress continued, NE levels were significantly lower in the brainstem, and eventually in the hypothalamus, of stressed animals. The relationship of these observations to environmentally-induced hypertension is discussed.

Animals↗

PubMed1989

Bilateral renal denervation can prevent the development of stress-induced hypertension in the borderline hypertensive rat.

The borderline hypertensive rat (BHR) shows large blood pressure responses to either stress or a high salt diet. Since the renal nerves have been shown to play a role in several animal models of hypertension, the current study sought to determine the effect of bilateral renal denervation on the development of stress-induced hypertension in the BHR. BHR were deprived of renal nerves under ether anesthesia after either 5 or 11 weeks of daily 2-hour stress sessions. Additional BHR received sham surgery. Unstressed BHR, age-matched to stressed groups, received denervation or sham surgery. Following a 3 week recovery period, the protocol (stress or no stress) was continued for 10 additional weeks. Tail cuff systolic blood pressures were obtained weekly. BHR stressed for 5 weeks prior to denervation failed to develop hypertension in response to continued stress. Although BHR stressed for 11 weeks prior to denervation showed a temporary reduction in pressure following denervation, blood pressure returned to the hypertensive levels of sham-operated controls after several weeks. Thus, there may be a critical period during which the renal nerves are necessary for the expression of stress-induced hypertension in the BHR. These observations are discussed in relation to the effects of renal denervation on hypertension in various animal models.

Animals↗

PubMed1988

Lithium chloride stabilizes systolic blood pressure and increases adrenal catecholamines in the spontaneously hypertensive rat.

The effects of daily, intraperitoneal injections of LiCl (3 mEq/kg) on systolic blood pressure (SBP) and adrenal catecholamine levels were measured in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Control animals from each strain were injected with equivalent volumes (0.1 ml/100 g b.wt.) of 0.9% saline (0.15 mEq/kg). SBP in LiCl-treated SHR was significantly lower (p less than 0.05) than that of saline-treated SHR (177 +/- 7 vs. 196 +/- 4 mm Hg, respectively) after one week. After two weeks SBP was lower in LiCl SHR than in saline controls, but this difference was not significant. While SBP of both LiCl and saline treated WKY was not significantly different (146 +/- 4 vs. 147 +/- 8 mm Hg, respectively), SBP in both WKY groups remained lower than the SBP for either group of SHR. LiCl induced a significant weight loss in the SHR, but not in the WKY. Adrenal norepinephrine and epinephrine were significantly (p less than 0.05) higher in LiCl-treated rats of both strains; dopamine was also higher in LiCl-treated rats of both strains, but significant only between SHR-LiCl and SHR controls. It appears that LiCl's effect in slowing the development of hypertension is independent of its action on adrenal catecholamines. The SHR's increased sensitivity to LiCl, relative to weight loss and SBP, may reflect differences in genetic or physiological status of the animal compared to WKY. These differences may be associated with alterations in membrane ion transport systems.

Adrenal Medulla↗

PubMed1988

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.

Animals↗

PubMed1988

Cardiovascular and renal responses to stress in borderline hypertensive rat.

Wistar-Kyoto (WKY) and borderline hypertensive rats (BHR) were exposed to either a normal or high-sodium chloride (NaCl) diet for 8 wk. Cardiovascular and renal data were collected from arterial and bladder catheters, respectively, in conscious animals during control and stress (aversive classical conditioning) sessions. Results indicated that BHR on a high-NaCl diet exhibited no increase in blood pressure in response to stress compared with BHR on a normal diet. A high-NaCl diet diminished the recovery of blood pressure to base line during stress in WKY compared with normal NaCl controls. Also, a high-NaCl diet and stress interacted in the BHR to decrease sodium excretion and renal plasma flow during stress compared with the control session (3.8 vs. 4.8 mueq.min-1.100 g body wt-1; 3.6 vs. 4.0 ml.min-1. 100 g body wt-1, respectively). Finally, increased dietary NaCl blunted the norepinephrine response to stress in WKY but not in BHR (263 vs. 767 pg/ml). These data suggest that the interaction of genetic and environmental factors are important variables for the development of hypertension.

Animals↗

PubMed1988

Aerobic power and cardiovascular response to stress.

The relationship between aerobic fitness as measured by maximal O2 uptake (VO2max) and the cardiovascular response to laboratory stressors was examined in two experiments. First, 34 male college students were screened on the basis of their heart rate (HR) response to a reaction time-shock avoidance (RT-AV) task. The six individuals showing an average HR increase of 45 beats/min (reactives) and the six subjects showing an average increase of 8 beats/min (nonreactives) did not differ in VO2max (47.7 +/- 2 vs. 48.7 +/- 1 ml.kg-1.min-1, respectively). However, a statistically significant association between a reported family history of hypertension and peak HR response to RT-AV was seen. In the second series of experiments, the plasma catecholamine and cardiovascular responses of eight elite endurance-trained athletes (VO2max 70.6 +/- 1 ml.kg-1.min-1) and eight untrained volunteers (VO2max 45.5 +/- 1 ml.kg-1.min-1) were compared on the following: RT-AV, reaction time for monetary reward (RT-AP), cold pressor, isometric handgrip, and orthostatic challenge (standing). The trained group exhibited a significantly lower mean HR at rest (P less than 0.05), otherwise there were no significant differences between the two groups. The results indicate that although individual differences (e.g., family history of hypertension and high resting HR) can be related to the potential for cardiovascular responses to novel laboratory challenges, the contribution of fitness to this characteristic is much less clear. Further exploration of questions pertaining to fitness and stress should focus on individuals with a predisposition to stress reactivity.

Adult↗

PubMed1987

Hypertension produced by a high sodium diet in the borderline hypertensive rat (BHR).

The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made. Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension.

Animals↗

PubMed1986

The effects of intracerebroventricular injection of clonidine on conditioned pressor and adrenergic responses in rats.

Studies from this laboratory have shown that the first filial offspring of female spontaneously-hypertensive rats and male Wistar-Kyoto (WKY) normotensive rats develop stress-induced hypertension. The present study sought to examine the effects of intracerebroventricular administration of clonidine (8 micrograms) on cardiovascular and sympathoadrenal responses to aversive classical conditioning in these borderline hypertensive rats (BHR) and in normotensive WKY control rats. Clonidine caused significant reductions in resting arterial pressure, vascular resistance, heart rate and concentrations of epinephrine (E) in plasma for both hypertensive and normotensive rats. Central administration of normal saline to control rats of each strain did not alter basal cardiovascular or sympathoadrenal function. The presentation of a conditioned stimulus (CS) elicited a significant increase in arterial pressure and total peripheral resistance in hypertensive rats treated with saline and clonidine and in normotensive rats treated with saline. In contrast, normotensive rats treated with clonidine showed no increases in arterial pressure or vascular resistance following the onset of the conditioned stimulus. The aversive conditioning session instigated significant increases in the concentrations of norepinephrine (NE) and E in plasma in saline-treated rats. Hypertensive and normotensive rats treated with clonidine-showed a blunted increase in plasma concentrations of NE and E during this period; however, concentrations of E in hypertensive rats increased significantly from the baseline period after injection. These data suggest that an abnormality in central alpha 2-adrenoceptor-mediated inhibition of sympathoadrenal discharge and sympathetic vasomotor tone may predispose the hypertensive rat to develop stress-induced hypertension.

Animals↗