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Nineteen children born to patients with panic disorder and a comparison group of 16 children born to unaffected, non-psychiatric patient subjects exposed to novel and mildly stressful situations (visiting an unfamiliar place and watching a movie containing anxiogenic scenes) were assessed for their behaviors, heart rate, respiratory rate and salivary cortisol secretion. At arrival children born to patients with panic disorder had significantly longer latency of first spontaneous verbal comment, fewer prosocial behavior, and increased distress and attachment behavior. During the projection of the movie, children of the two groups differed for attachment, distress, and exploration behaviors. During the anxiogenic scenes children born to patients with panic disorder showed increased behavioral inhibition and higher heart rate. Autonomic modulation, respiratory rates and cortisol secretion were similar in the two groups. Some distinct psychophysiological patterns may constitute early manifestations of the transmitted liability to panic disorder.

At a cellular level, cardiac pacemaking, which sets the rate and rhythm of the heartbeat, is produced by the slow membrane depolarization that occurs between action potentials. Several ionic currents could account for this pacemaker potential, but their relative prominence is controversial, and it is not known which ones actually play a pacemaking role in vivo. To correlate currents in individual heart cells with the rhythmic properties of the intact heart, we have examined slow mo (smo), a recessive mutation we discovered in the zebrafish Danio rerio. This mutation causes a reduced heart rate in the embryo, a property we can quantitate because the embryo is transparent. We developed methods for culture of cardiocytes from zebrafish embryos and found that, even in culture, cells from smo continue to beat relatively slowly. By patch-clamp analysis, we discovered that a large repertoire of cardiac currents noted in other species are present in these cultured cells, including sodium, T-type, and L-type calcium and several potassium currents, all of which appear normal in the mutant. The only abnormality appears to be in a hyperpolarization-activated inward current with the properties of Ih, a current described previously in the nervous system, pacemaker, and other cardiac tissue. smo cardiomyocytes have a reduction in Ih that appears to result from severe diminution of one kinetic component of the Ih current. This provides strong evidence that Ih is an important contributor to the pacemaking behavior of the intact heart.

Cardiovascular abnormalities are prominent in the genetic disorder, familial dysautonomia (FD). To determine if autonomic dysfunction involves cardiac, as well as peripheral vascular integrity, noninvasive tests were performed in 10 FD patients and 8 healthy control subjects while supine and at 90 degrees tilt. Simultaneous blood pressure (BP) and heart rate (HR) and QTc were obtained, while performing signal-averaged electrocardiography (SAECG) and heart rate variability (HRV). FD subjects were tested on 2 separate days, before and 1 h after oral fludrocortisone or midodrine; controls were tested once without medication. With tilt, all FD subjects decreased mean BP > or = 24 mm Hg by 5 min. On SAECG, 70% of supine FD subjects had a prolonged tQRS; only 2 FD subjects shortened tQRS with tilt. The QTc interval was prolonged (> 440 ms) in 2 supine FD subjects; with tilt, the QTc prolonged in a third. Frequency domain analysis of HRV revealed that mid (MF) and high frequency band areas were significantly decreased when supine, but not when upright. On time domain analysis, the pNN50 was significantly decreased in FD subjects (8.9 +/- 1.7 vs. 17.7 +/- 3.6%, p < 0.01). Fludrocortisone lowered supine BP and HR and increased supine MF area. Midodrine raised supine and erect BP, lowered erect HR, and shortened erect QTc. Although all FD subjects have abnormal orthostatic BP and HR responses, cardiac tone, as assessed by electrocardiographic and HRV responses, varies. Prolongation of the tQRS appears to be a sensitive but not specific indicator of autonomic dysfunction. QTc prolongation may indicate more extensive sympathetic dysfunction. HRV data suggest some FD patients have abnormalities in parasympathetic, as well as sympathetic, cardiac tone.

The heart of Drosophila melanogaster is a simple muscular tube with a posterior pulsatile portion and a thoracic-cranial vessel. The pacemaker, located caudally, is myogenic. Its rate of firing is modulated by neurotransmitters. Serotonin, octopamine, norepinephrine, dopamine, and acetylcholine accelerate the heart, in that order of potency. Dihydroxyphenylalanine, gamma-aminobutyric acid, glutamate, and glycine have no effect. Generally, the regularity of the heartbeat is not adversely affected by treatment with any of these neurotransmitters. We show here that amnesiac, a neurological mutation, and Dihydroxyphenylalanine decarboxylasetemperature sensitive, a mutation that interferes with synthesis of dopamine, norepinephrine, and serotonin, result in slower heart rate and reduced regularity across a normal range of temperatures for these flies. Dopamine-N-acetyltransferase, which is on the catabolic route to dopamine, serotonin, and octopamine, has no effect. hypoactiveC reduces the rate of the heart, but its mechanism of action is unknown.

Objectives: We sought to analyze age-gender differences in the rate-corrected QT (QTc) interval in the presence of a QT-prolonging gene., Background: Compared with men, women exhibit a longer QTc interval and an increased propensity toward torsade de pointes. In normal subjects, the QTc gender difference reflects QTc interval shortening in men during adolescence., Methods: QTc intervals were analyzed according to age (< 16 or > or = 16 years) and gender in 460 genotyped blood relatives from families with long QT syndrome linked to chromosome 11p (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53)., Results: The mean QTc interval in genotype-negative blood relatives (n = 240) was shortest in men, but similar among women, boys and girls. For genotype-positive blood relatives, men exhibited the shortest mean QTc interval in chromosome 7q- and 11p-linked blood relatives (n = 194), but not in the smaller 3p-linked group (n = 26). Among pooled 7q- and 11p-linked blood relatives, multiple regression analysis identified both genotype (p < 0.001) and age-gender group (men vs. women/children; p < 0.001) as significant predictors of the QTc interval; and heart rate (p < 0.001), genotype (p < 0.001) and age-gender group (p = 0.01) as significant predictors of the absolute QT interval. A shorter mean QT interval in men was most evident for heart rates < 60 beats/min., Conclusions: In familial long QT syndrome linked to either chromosome 7q or 11p, men exhibit shorter mean QTc values than both women and children, for both genotype-positive and -negative blood relatives. Thus, adult gender differences in propensity toward torsade de pointes may reflect the relatively greater presence in men of a factor that blunts QT prolongation responses, especially at slow heart rates.

A common polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice) is associated with differences in circulating ACE levels that may confer a differential risk for cardiovascular diseases. To study the effects of genetically determined changes in Ace gene function within a defined genetic and environmental background, we have studied mice having one, two, or three functional copies of the Ace gene at its normal chromosomal location. ACE activities in the serum increased progressively from 62% of normal in the one-copy animals to 144% of normal in the three-copy animals (P < 10(-15), n = 132). The blood pressures of the mice having from one to three copies of the Ace gene did not differ significantly, but the heart rates, heart weights, and renal tubulointerstitial volumes decreased significantly with increasing Ace gene copy number. The level of kidney renin mRNA in the one-copy mice was increased to 129 +/- 9% relative to that of the normal two-copy mice (100 +/- 4%, P = .01, n = 16). We conclude that significant homeostatic adaptations successfully normalize the blood pressures of mice that have quantitative changes in Ace gene function. Our results suggest only that quantitative changes in expression of the Ace gene will observably affect blood pressures when accompanied by additional environmental or genetic factors that together with Ace exceed the capacity of the homeostatic mechanisms.

In a screen for early developmental mutants of the zebrafish, we have identified mutations specifically affecting the internal organs. We identified 53 mutations affecting the cardiovascular system. Nine of them affect specific landmarks of heart morphogenesis. Mutations in four genes cause a failure in the fusion of the bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart venticle is visible and the atrium is directly fused to the outflow tract. In the overlooped mutant, the relative position of the two heart chambers is distorted. The heart is enormously enlarged in the santa mutant. In two mutants, scotch tape and superglue, the cardiac jelly between the two layers of the heart is significantly reduced. We also identified a number of mutations affecting the function of the heart. The mutations affecting heart function can be subdivided into two groups, one affecting heart contraction and another affecting the rhythm of the heart beat. Among the contractility group of mutants are 5 with no heart beat at all and 15 with a reduced heart beat of one or both chambers. 6 mutations are in the rhythmicity group and specifically affect the beating pattern of the heart. Mutations in two genes, bypass and kurzschluss, cause specific defects in the circulatory system. In addition to the heart mutants, we identified 23 mutations affecting the integrity of the liver, the intestine or the kidney. In this report, we demonstrate that it is feasible to screen for genes specific for the patterning or function of certain internal organs in the zebrafish. The mutations presented here could serve as an entry point to the establishment of a genetic hierarchy underlying organogenesis.

Susceptibility to alcoholism varies with age, gender, and familial background. Youthful nonalcoholic males with multigenerational family histories of male alcoholism seem at particular risk. Previous investigations suggest that such males are characterized by abnormal psychophysiological response, while sober and alcohol-intoxicated; additional recent studies indicate that the endogenous opiate systems are involved in mediating ethanol reinforcement and modulating intake. We first compared cardiac response to alcohol administration among young (mean = 22.8 years), nonalcoholic men and women with multigenerational, unigenerational, and negative family histories of alcohol dependence and abuse. Then, we compared the ethanol-induced cardiac response of the males in these three groups to that of currently alcohol-dependent older males and age-matched nonalcoholic male controls. Finally, we examined ethanol-induced change in plasma beta-endorphin and cortisol levels among a subset of the nonalcoholic males, divided into those with high and low levels of postethanol administration heart-rate increase. Nonalcoholic males with multigenerational family histories of male alcoholism were characterized by significantly higher [t(301) = 5.70, p < 0.0001, Cohen's d = 0.73] levels of ethanol-induced heart-rate increase than nonalcoholics from all other comparison groups. The magnitude of their increase matched that of current male alcohol-dependents. Nonalcoholic males with high levels of ethanol-induced heart-rate increase also produced significantly more plasma beta-endorphin after consuming alcohol. Peak production of beta-endorphin was highly correlated (r = 0.861, p < 0.001) with magnitude of heart-rate increase. A subset of those at risk for alcoholism may be characterized by sensitivity to ethanol-induced reward, marked by heightened ethanol-induced, heart-rate increase, mediated by ethanol stimulation of endogenous opiate production. This subset might contain those who, once alcoholic, would differentially benefit from treatment with opiate antagonists.

As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system. The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined. We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function. Nine mutations clearly disrupt the formation of the heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility. Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia. Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart. We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites. In terms of cardiac function, one large group exhibits a weak beat. In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle. Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction. In several other mutants, regurgitation of blood flow from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction. The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature.

The objective of this study was to examine associations in youth between antisocial behavior and cardiovascular profile. Younger brothers of adjudicated delinquents (N = 120) received a standardized psychiatric assessment and an assessment of three factors often studied in behavioral cardiology research: family history of hypertension, resting blood pressure, and obesity. As a group, relative to population norms, these youth exhibited signs of obesity and elevated blood pressure, with 30% of the sample appearing clinically obese and 24% having a blood pressure above the 90th percentile for national norms in their age cohort. Within the sample, score on the Child Behavior Checklist (CBCL) Delinquency scale correlated with blood pressure (r = .29-.34) and an index of obesity, weight/height3 (r = .20). Further, scores on the CBCL Delinquency, Aggression, and Externalizing scales were elevated in boys with a positive family history of hypertension. Among boys at risk for delinquency, disruptive psychopathology relates to factors often studied in behavioral cardiology research. Relationships between risk factors for ischemic cardiovascular disease and hostile behavior may be manifested with measures of disruptive psychopathology.

The authors tested the hypothesis of a genetic influence on heart rate variability (HRV). This genetic influence was assessed in 62, twin pairs (30 monozygotic, 32 dizygotic). From all twins, long-term electrocardiographic records were obtained, edited, and analyzed. Heart rate variability analysis was performed on the basis of parameters from time-domain, frequency-domain, and nonlinear dynamics. First, the parameter distances between the two twins of a pair and between one of the two and a third randomly selected person of another age-matched twin pair (ST1) were compared. Second, the parameter distances between the two twins and the averaged parameter distances of these two twins to all other age-matched persons (ST2) were compared. Finally, the averaged differences in parameter values between monozygotic and dizygotic age-matched twin pairs were compared. For statistical analysis, the nonparametric Wilcoxon's matched-pair signed rank test and parametric t-test for paired samples were used. Twin pairs show a significant lower difference in parameter values than other randomly selected and age-matched couples (P < .001 in ST1 and ST2). This reflects a considerable familial influence. Most parameters of the time-domain, none of the frequency-domain, and half of the nonlinear dynamics show significant differences between twin pairs and nontwin pairs. As a result of the comparison between monozygotic and dizygotic twin pairs, a significant lower parameter difference in the monozygotic pairs (P < .05) is found. These results suggest that there is a genetic component in heart rate generation and HRV, in addition to family environmental influences. Analysis of HRV might become a useful method in phenotyping severe genetic changes in cardiovascular diseases.

The mutation no action potential (nap) induces arrhythmia in the heartbeat of Drosophila melanogaster larvae at temperatures above 20 degrees C; heartbeat becomes normally rhythmic again after a shift back to 20 degrees C. For this phenotype, napa is almost completely recessive to the wild type, napa also reduces the temperature-sensitivity of heart rate over a wide range of temperature, for this phenotype, napa is dominant over the wild type, napa causes reversible paralysis in adults by epistatic effects on the expression of paralyrica, a gene encoding a voltage-dependent sodium channel. However, the paramutation, which induces paralysis in adults at 29 degrees C, has no effect on larval heartbeat at temperatures between 20 degrees and 37.5 degrees C. The period gene, contra earlier reports, has no effect on heartbeat.

The genetic influence of ambulatory blood pressure and heart rate was examined in 38 pairs of monozygotic twins, 17 pairs of same-sex dizygotic twins, and 11 pairs of opposite-sex dizygotic twins, all aged 15 or 17 years. The data were analyzed taking into consideration that the response was multivariate (24-h values) instead of the usual univariate response. The results demonstrated the heritability of ambulatory blood pressure and heart rate. This was true regardless of whether the estimate of heritability involved monozygotic twin pairs compared to same-sex dizygotic twin pairs only, or all dizygotic twin pairs. The time-related intraclass correlation coefficient within each twin classification indicated that the patterns of response within twin pairs correlated more for monozygotic twin pairs than within twin pairs for either set of dizygotic twin pairs. In addition, although the opposite-sex dizygotic twin pairs may have different mean levels of response, they exhibit a similarity of patterns of response akin to that seen within same-sex dizygotic twin pairs.

Little is known about racial differences in cardiovascular responses to postural change. The immediate and delayed change from sitting to standing was studied in 207 healthy young Asian, black, and white men and women by means of a noninvasive blood pressure tracking system. Whereas Asians and whites had decreased mean arterial pressure (MAP) 32-41 s after standing, blacks had an increase. During the delayed response (3 min after standing), compared to Asians and whites, blacks had greater increases in diastolic blood pressure and MAP. Their heart rate increase was also greater than Asians. For systolic blood pressure and pulse pressure there were Race x Family History interactions for the immediate response to orthostasis and Race x Gender interactions for the delayed response. Blacks generally displayed different cardiovascular patterns from the other two racial groups, possibly reflecting increased peripheral resistance and altered baroreceptor function.

Reduced heart rate variability (HRV) has a strong predictive value in terms of sudden death, as compared to other prognostic criteria, but it has never been previously studied in experimental models of cardiac hypertrophy and failure. However, it has been quantified in rats using Holter monitoring and the peak and trough method of analysis. In normal rats, as in humans, short and long oscillations, sensitive, respectively, to atropine and propranolol were detected. Both correlate with heart rate. Cardiothyrotoxicosis was characterized by tachycardia and, independently, by a pronounced alteration in long oscillations. HRV was normal in compensatory cardiac hypertrophy due to aortic stenosis, but in this model the normal correlation existing between HRV and heart rate had disappeared. It is suggested that the main determinants of the above modifications of HRV are the changes in the new myocardial phenotype observed in terms of beta-adrenoceptor and muscarinic densities.

This study investigated the acute effects of ethanol (0.25, 0.5, or 1 g/kg, iv) on mean arterial pressure, heart rate, and gain of the baroreceptor reflex control of heart rate (BRS) in conscious spontaneously hypertensive rats (SHRs) and age-matched Wistar rats. BRS was substantially lower in the SHRs as compared with the Wistar rats when measured by phenylephrine (-0.95 +/- 0.16 vs. -2.02 +/- 0.22 beats/min/mm Hg) or nitroprusside (-1.90 +/- 0.2 vs -3.02 +/- 0.32 beats/min/mm Hg). None of the doses of ethanol influenced BRS in the SHR. In contrast, ethanol attenuated BRS in Wistar rats, but this effect was dependent on the dose used and the type of response. The lower doses attenuated the reflex tachycardic response, but had no effect on the reflex bradycardic response. On the other hand, the 1 g/kg dose of ethanol attenuated the reflex bradycardic but not the tachycardic response. Ethanol produced a pressor effect (15-25 mm Hg; 5-min duration), which was neither dose- nor strain-dependent. However, only in the SHR mean arterial pressure remained elevated (10-15 mm Hg above control) for 20 min in response to the 0.5 g/kg dose of ethanol, and its recovery coincided with the occurrence of a slowly developing negative chronotropic response. Ethanol produced a dose-related negative chronotropic effect in both strains of rats that was of longer duration in the SHR, particularly with the 1 g/kg dose. It is possible that the bradycardic effect of ethanol influenced negatively its pressor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure and heart rate reactions of 182 confirmed offspring of normotensive (110 female, 72 male) and 112 offspring of hypertensive (66 female, 46 male) individuals to the stressor of blood donation were examined. Subjects were tested at two sites, one in the United States and one in Canada. Although influenced by site, young normotensive offspring of hypertensives generally exhibited significantly greater blood pressure levels in anticipation of donating blood than offspring of normotensives. The higher reactivity of offspring of hypertensives observed in stressful laboratory settings may generalize to more ecologically valid settings, even those which, like blood donation, require passive coping efforts.

The existence of a relationship between cardiovascular reactivity to signalled shock and alcohol consumption can be inferred from studies of males at increased familial risk for alcoholism. The present study examined two groups of nonalcoholic men--those with multigenerational histories (MGH) of alcoholism and family--history negative (FH-) controls-to determine whether reactivity was related to voluntary ethanol consumption in the context of a beverage taste test. High reactors, a significant majority of whom were MGH males, drank significantly more vodka and orange juice, rum and coke, and orange juice when asked to rate the flavor of three alcoholic and two nonalcoholic drinks. High reactors also consumed more alcohol on a weekly basis according to their self-report.

The present study examined whether inconsistent findings for elevated cardiovascular response to stress in female offspring of hypertensives might be a function of 1) lack of control for menstrual cycle phase, and 2) stressor type employed. Thirty healthy women (18-35 years), half of whom were offspring of hypertensives, were tested in both the luteal and follicular phases of the menstrual cycle. Order of testing was counterbalanced between subjects and cycle phase was confirmed by measurement of serum sex hormone levels. In each session, subjects were exposed to four tasks: the cold pressor test, interpersonal speech, shock-avoidance video-game, and reading. The most consistent menstrual cycle effect was for offspring of normotensives who exhibited higher diastolic blood pressure and state-anger responses to the speech task in the follicular compared with the luteal phase. Though menstrual cycle had no consistent effect on offspring of hypertensives, their luteal phase diastolic blood pressure and state-anger responses to the speech task were elevated compared with controls. Potential limitations of the observed familial differences in luteal phase response are discussed.

Two hundred healthy adolescent to middle-aged individuals (12-44 years, M = 20 years) were tested in a standardized stress protocol. These individuals comprised 20 monozygotic female, 20 monozygotic male, 20 same-sex dizygotic female, 20 same-sex dizygotic male, and 20 opposite-sex dizygotic twin pairs. Familial influences on heart rate, blood pressure, and self-report anxiety responses to four different kinds of stressors (Visual-Verbal Test for Conceptual Thought, mental arithmetic, isometric handgrip, cold pressor) were assessed using biometrical genetic model fitting. Evidence of significant genetic effects on resting heart rate and blood pressure was obtained, providing heritability estimates of .65, .63, and .58 for resting heart rate and systolic and diastolic blood pressure, respectively. Cardiovascular reactivity to the Visual-Verbal Test, mental arithmetic, and the cold pressor test appeared to be primarily influenced by genetic and idiosyncratic (nonfamilial) environmental factors, whereas reactivity to handgrip was more related to effects of the family environment. The results of multivariate model fitting suggested that the genetic effects on reactivity were relatively independent of those affecting resting heart rate and blood pressure and that there was significant overlap of genetic influences on heart rate and blood pressure responses to the two active coping tasks.

24-hour ambulatory blood pressure (BP) was monitored by non-invasive methods in 42 offspring of hypertensive families (age [mean (SD1)] 40(7) years) and 38 offspring of normotensive families (age 33(6) years). The family history was defined according to parental BP data from two surveys conducted 27 years apart. Casual BP was 137(17)/84(12) mmHg in offspring of hypertensive families and 117(9)/69(6) mmHg in offspring of normotensive families (difference: p < 0.001). Average 24-h BP was 123(10)/74(6) mmHg and 113(8)/65(5) mmHg, respectively (difference: p < 0.001). The systolic and diastolic BP difference of approximately 10 mmHg was observed between the groups throughout the monitoring period. Hypertension--defined according to a recent meta-analysis as an average 24-h BP > or = 139/87 mmHg--was found in 6 offspring of hypertensive families and in no offspring of normotensive families (p < 0.05). The 24-h systolic and diastolic BP load--the percentage of readings above 140/90 mmHg (day-time) and 120/80 mmHg (night-time)--was higher in offspring of hypertensive than normotensive families (27%/17% vs. 7%4%; p < 0.001). After adjustment for intrafamilial covariation, age, and other possibly confounding variables, the differences between the groups remained. The present findings suggest that BP in subjects with a family history of hypertension is elevated on a permanent basis, and not only when it is measured in the doctor's office.

Sixty boys aged 12-16 took part in an experiment in which physiological and subjective measures were obtained at rest and in response to mental arithmetic and mirror drawing tasks. Blood pressure was recorded from biological parents, and subjects were subsequently categorized as being at high family risk for cardiovascular disease if either parent had a history of coronary heart disease or hypertension, or a resting blood pressure > or = 140/85 mmHg. Twenty boys were classified as high family risk and forty as low risk. A significant interaction between family risk and a disposition towards anger inhibition was observed, with the greatest systolic blood pressure responses to tasks being recorded in high risk boys who reported high levels of anger inhibition. This effect was maintained after controlling for initial blood pressure level, age and body mass. The cardiac baroreceptor reflex was inhibited during tasks, and was lower in high than low family risk subjects. The results suggest that the tendency to inhibit anger expression interacts with familial factors in determining reactivity patterns that may be indicative of raised risk of future cardiovascular disease.

College-age subjects with and without a parental history of hypertension completed a battery of tests of cognitive function on two separate occasions. Pulse rate and blood pressure were measured during performance of each task. In one session, subjects were told that their performance was being evaluated and videotaped from behind an observation mirror (Evaluation Condition). In the other session, subjects were told that their performance was not being observed (Nonevaluation Condition). Regardless of Evaluation Condition, Parental History subjects exhibited slower search of short-term memory than Non-Family History subjects during the first but not the second testing session. Parental History subjects displayed greater elevations in pulse rate than Nonparental History subjects during task performance. The results were interpreted as providing evidence that pathophysiological mechanisms associated with essential hypertension are not the only viable explanations of lower levels of cognitive performance exhibited by hypertensive subjects.

Seven White Carneau (WC) pigeon families of the high blood pressure (HBP) line with 51 offspring and six families of the low blood pressure (LBP) line with 57 offspring were used to estimate heritability of the blood pressure trait. Pigeons from the HBP line had significantly higher systolic blood pressures than the LBP line at ages 1 through 6 months. No significant effect of age on blood pressure was observed in either the HBP line or the LBP line. Systolic, diastolic and mean arterial pressures were 155 +/- 6.4 and 122 +/- 5.7 and 139 +/- 6.1, respectively, for male parents and 163 +/- 9.3 and 125 +/- 7.1 and 143 +/- 8.3, respectively for female parents. The mid-parent mean averaged across pairs was 159 +/- 7.3 and 123 +/- 5.9, and 141 +/- 6.6, for systolic, diastolic, and mean arterial pressures, respectively. The average systolic, diastolic, and mean arterial pressures for offspring were 159 +/- 5.9, 132 +/- 5.5, and 147 +/- 5.6, respectively. Blood pressure measurements did not differ greatly between the offspring and the mid-parent mean, indicating that offspring inherit blood pressure levels similar to those of their parents. Mean heart rates were 189 +/- 12.2, 202 +/- 14.2 and 197 +/- 9.9 for the male parents, female parents and offspring, respectively. Heritability estimated by the regression of offspring on the mid-parent mean was 0.55 +/- 0.18, 0.69 +/- 0.19 and 0.61 +/- 0.18, 0.82 +/- 0.19 for systolic, diastolic and mean arterial pressure and heart rate, respectively. The results suggest that genetic factors play a significant role in influencing blood pressure in WC pigeons.

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.

The present study investigated whether subjects with a positive family history of hypertension would display differential responses in blood pressure and heart rate across different laboratory tasks. We also wanted to know whether subjects would display stable within-subject responses across different laboratory tasks. Twenty-three family history positive subjects and 23 with a negative family history participated in three tasks: 1) mental arithmetic, 2) a conversation about the weather (low affect task), and 3) a conversation about a recent upsetting, interpersonal event (high affect task). Positive family history was associated with elevated diastolic resting blood pressure and greater diastolic responsivity overall. For both groups, arithmetic was associated with the greatest heart rate changes, whereas the distressing conversation was accompanied by the greatest diastolic blood pressure response. Stability of cardiovascular activation across different tasks was present only for heart rate; it was weak for diastolic blood pressure, and completely absent for systolic blood pressure.

Heart rate was recorded from male siblings over the age of 30 who were members or either alcoholic or control families. Brothers from alcoholic families included both those with a diagnosis of alcoholism (n = 66) and those without such a diagnosis (n = 18). Control brothers (n = 33) were chosen for absences of any Axis I psychopathology including alcoholism in all first- and second-degree relatives. Subjects were engaged in two auditory tasks. All subjects were presented with high- and low-pitched tones with varying probabilities. In the first task (counting), subjects were told to count only the number of high tones. In the second task (choice reaction), subjects were asked to perform a simple motor response to each high or low tone. Prestimulus levels, anticipatory deceleration and acceleration were compared between the three groups. All members of the affected families, whether alcoholic themselves or not, were found to have a significantly higher baseline heart rate than members of control families. In addition, differences in the anticipatory deceleration were greater in control brothers than in brothers from the affected families for the counting task.

Data collected from 95 nonalcoholic men who had either a multigenerational (MFH), unigenerational (UFH), or negative family history (FHN) of alcoholism were subjected to a discriminant function analysis to determine how well a set of variables differentiated between the family history groups. The data-set comprised personality measures (sensation seeking scales, neuroticism, and extroversion), measures of cardiovascular reactivity to unavoidable shock, and measures of the cardiovascular reactivity-dampening effects of alcohol. The discriminant analyses correctly classified 62% of all subjects, 75% of MFH subjects, 47% of UFH subjects, and 63% of FHN subjects. A canonical discriminant function analysis revealed one significant dimension (canonical variable) that differentiated between family history groups. The high density (MFH) family group scored positively on this dimension, while the UFH and FHN groups had negative mean scores on this variable. A MFH of alcoholism was characterized by a pattern of increased sensitivity to the cardiovascular reactivity-dampening effect of alcohol, cardiovascular hyperreactivity to unavoidable shock when sober, and the personality characteristic of experience seeking, which is associated with a desire for novel and unconventional experiences.

Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18-year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity.

The influence of maternal environment on the development of high blood pressure in spontaneously hypertensive (SHR) and Dahl salt-sensitive (SS/Jr) rats was examined using the technique of reciprocal cross-fostering. Previous experiments from this laboratory demonstrated that adult blood pressures of the SHR and SS/Jr strains were significantly attenuated when hypertensive-strain pups were fostered to a dam of the respective normotensive control strain during the preweaning period. In this study, SHR and SS/Jr pups were assigned to either a cross-fostered (fostered to a dam of the opposite hypertensive strain) or control-reared condition within 24 h of birth. Adult resting blood pressures were similar in control and cross-fostered SHR rats and in control and cross-fostered SS/Jr rats. Heart rates and heart, adrenal, and kidney weights were also similar in control and cross-fostered rats of each strain. However, body weights of SHR rats reared by an SS/Jr dam were somewhat lower compared to control-reared SHR rats. These data indicate that the maternal environments provided by SHR and SS/Jr mothers are similar in some way such that they permit the development and full expression of the hypertensive phenotype in both same-strain and opposite-strain pups.

The present study examined the influence of trait anxiety on the cardiovascular responses of normotensive offspring of hypertensives and normotensives. Forty-eight young adult males, half of whom were offspring of hypertensives (PH+), were exposed to an extended active coping stressor. This was a 1 hr shock avoidance procedure with avoidance made contingent on video-game performance. Trait anxiety status interacted with parental history of hypertension in predicting cardiovascular response. PH+ subjects who scored high on trait anxiety exhibited greater elevations of heart rate and forearm blood flow, and decreases in forearm vascular resistance than did PH+/low trait anxiety subjects or offspring of normotensives (PH-). Cardiovascular responses of PH+/low trait anxiety subjects did not differ significantly from those of PH- subjects. Results suggest affective factors may moderate cardiovascular responses of individuals at risk for hypertension.

Examined hemodynamic activity--at rest, during mental arithmetic, and during hand cold pressor--in young men varying in risk for hypertension. Classification into low-risk (n = 72), moderate-risk (n = 20), and high-risk (n = 13) groups was based on resting systolic blood pressure (SBP) and parental history of essential hypertension (PH). Dependent variables were SBP, diastolic BP (DBP), heart rate, and rate-pressure product (RPP). Progressively greater hemodynamic activity was seen across risk groups at rest and during the tasks. Risk groups differed significantly in SBP, DBP, and RPP at baseline (ps less than .003) and in size of response to mental arithmetic (ps less than .05) but not to cold pressor. These relationships were either absent or weaker when using either risk factor alone to form risk groups. These findings suggest that hemodynamic reactivity to mental stress is predicted better by a combination of resting SBP and PH than by either risk factor alone and that physiological reactivity may be an important accompaniment of increased risk for hypertension.

The idiopathic long QT syndrome (LQTS) is an infrequently occurring disorder. It has major clinical impact as patients are prone to syncope, ventricular tachyarrhythmias and sudden arrhythmogenic cardiac death. This paper reports the value of ambulatory electrocardiogram (ECG) monitoring as a diagnostic tool to establish the diagnosis of LQTS. 14 patient with idiopathic LQTS were studied. The results were compared to those of 14 age- and sex-matched healthy control individuals. A 24-hour ambulatory ECG tracing was obtained in each individual. 5/14 patients with LQTS had pathological findings during ambulatory ECG monitoring (2 patients with episodes of torsade de pointes tachycardia, 2 patients with T-wave alternans and 1 patient with bradycardia due to an intermittent SA block), whereas all control persons had normal ambulatory ECG recordings (p < 0.03). Thus, ambulatory ECG recordings may contribute significant diagnostic information in patients with suspected LQTS.

Genetic and maternal influences on hypertension were studied by comparing the SHR and SS/Jr inbred rat strains and their reciprocal F1 hybrids under identical conditions. When raised on a low salt (LS) diet (0.3% NaCl), SHR rats had higher systolic blood pressure (SBP) than SS/Jr rats by 9 weeks of age. Direct recordings from freely moving rats at 18-24 weeks confirmed this difference. Placement on a high salt (HS) diet (8% NaCl) at 5 weeks of age significantly increased SBP within 3 weeks in all groups, although the degree of increment was significantly smaller in SHR females. Inbred strains had higher SBP than their F1 hybrids when measured indirectly and directly from arterial cannulae. After exposure to HS diet, F1 females reared by SHR dams exhibited larger increments in SBP, greater weight loss, and greater debilitation and associated mortality than F1 females reared by SS/Jr dams. Differences between inbred strains and F1s maintained on LS diet were consistent with dominance for low BP, and differential genetic control of hypertension in each inbred strain. F1 differences demonstrated that maternal factors affected body weight in weanlings, pressor response to HS diet, and associated debilitation.

The forearm blood flow (FABF) and other cardiovascular responses of 20 black men with a parental history of hypertension were compared with the responses of 18 black men without a parental history of hypertension. The results showed that sons of hypertensive parents had higher systolic (SBP) and diastolic (DBP) blood pressure than sons of normotensive parents during the initial assessment as well as significantly higher self-determined home SBP. Sons of hypertensive parents had higher SBP responses than sons of normotensive parents during mental challenge and the cold pressor, but there were no group differences in DBP, heart rate (HR), (FABF), or forearm vascular resistance (FAVR) responses to the stressors. Significant positive correlations between HR and FABF responses to the stressors were observed for sons of hypertensive parents. Finally, the results showed that the BP and FAVR responses to the cold pressor (a painful task that elicits alpha-adrenergic activity) were significantly higher than responses to mental challenge (a task that elicits beta-adrenergic activity) for both groups. The implications of these results are discussed in light of current research suggesting that blacks may have a greater tendency toward BP responses mediated by alpha-adrenergic increases in vascular resistance.

The purpose of the present investigation was to examine the genetic contributions to cardiovascular reactivity in an adult cohort of male twins. A total of 47 monozygotic (MZ) twin pairs and 54 dizygotic (DZ) twin pairs, aged 59 to 69 years, were laboratory tested at four sites as part of the third examination of the National Heart, Lung, and Blood Institute Twin Study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded during two tasks, a mental arithmetic task involving serial subtraction and the cold pressor test. Significant cardiovascular responsivity was observed during both tasks as measured by substantial elevations in SBP, DBP, and HR from resting periods to task periods. Heritability estimates were statistically significant for SBP and DBP but not HR levels during pretask baseline periods and during both tasks. Genetic variance was maintained for blood pressure reactivity to the mental arithmetic task after adjustments for baseline and performance. No genetic variance for SBP or DBP reactivity to the cold pressor test was evident.

The similarities of 30 young (X = 26 years) and 30 middle-aged (X = 52 years) spouse pairs in behavioral and cardiovascular response to two experimental stressors were compared to assess the importance of shared home experiences in determining cardiovascular responsivity to stress. Familial environmental influences on reactivity should produce increasing similarity among family members with number of years lived together. Although pair members exhibited a number of behavioral similarities, some of which appeared to increase with number of years lived together, there were few similarities in heart rate and blood pressure response to stress. However, both young and middle-aged pairs exhibited significant similarities in systolic blood pressure response to isometric handgrip. The fact that similarities were observed in young as well as middle-aged spouse pairs suggests that assortative mating in regards to cardiovascular reactivity to stress may occur in some instances. As a result, some previous estimates of the heritability of cardiovascular reactivity to environmental stress may have been artificially low.