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Biomedical subjects

E M Krieger

Publications and source records attributed to E M Krieger.

At least 19 recordsLinked to original sources

Influence of cardiopulmonary reflex on the sympathetic activity during myocardial infarction.

The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.

Animals↗

Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) causes secondary hypertension. However, the reasons why the prevalence of hypertension among OSA patients varies widely (35-70%) are not clear. We sought to investigate the phenotypic characteristics of patients with and without hypertension among OSA patients who were matched for disease severity. We studied 152 OSA patients (76 normotensive and 76 hypertensive) diagnosed by polysomnography. Detailed phenotypic characteristics, including laboratorial analysis, were determined in all patients. Univariate analysis followed by multiple logistic regression analysis was used to identify variables that were independently associated with hypertension. The apnea-hypopnea index in normotensive and hypertensive patients was similar (48+/-26 and 48+/-26 events/h, respectively) as well as minimum arterial oxygen saturation (76+/-10 and 75+/-10%, respectively) and total sleep time with oxyhaemoglobin saturation <90% (25+/-25 and 28+/-26%, respectively). Hypertensive patients were older (57+/-11 vs 47+/-12 years; P<0.001), had a higher body mass index (BMI; 34+/-7 vs 30+/-5 kg/m(2); P<0.001), had a higher frequency of women (37 vs 8%; P<0.001), had a higher incidence of diabetes (25 vs 6%; P=0.002) and a higher family history of hypertension (75 vs 42%; P=0.01) than did the normotensive patients. Multiple logistic regression analysis indicated that age (P=0.004), familial history of hypertension (P=0.004), BMI (P=0.04) and female sex (P=0.03) were the independent variables associated with hypertension. We concluded that increasing age and BMI, familial history of hypertension as well as female gender are phenotypic characteristics associated with hypertension among OSA patients with similar disease severity.

Adult↗

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability.

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 +/- 0.46 vs 0.21 +/- 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 +/- 0.62 vs 0.28 +/- 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.

Animals↗

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy.

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Adult↗

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.

Animals↗

Dysregulation of peripheral and central chemoreflex responses in Chagas' heart disease patients without heart failure.

BACKGROUND: The peripheral and central chemoreflexes are important autonomic mechanisms for regulating breathing and cardiovascular function. Although pathological inflammatory infiltration of the peripheral chemoreceptors and central nervous system has been reported in Chagas' disease, functional evaluation of chemoreflexes has not yet been performed. METHODS AND RESULTS: The hypothesis that chemoreflex function is altered in patients with Chagas' heart disease (CH) but normal left ventricle function was tested in 12 CH patients and 13 matched control subjects. The ventilatory rate, minute ventilation, heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, and venous norepi-nephrine responses to hypoxia and hypercapnia were determined. During hypoxia, the decrease in oxygen saturation was smaller in CH patients, despite a similar ventilatory response between groups. Both groups showed an increase in heart rate during hypoxia, but this response was blunted in CH patients. Although the mean arterial pressure response to hypoxia was similar in both groups, forearm vascular resistance significantly decreased in control subjects while remaining unchanged in CH patients. Moreover, a significant increase in plasma norepinephrine levels elicited by stimulation of peripheral chemoreceptors was observed only in the CH group. During hypercapnia, the increase in minute ventilation was smaller in CH patients, who did not exhibit the increase in norepinephrine observed in control subjects. CONCLUSIONS: These data suggest that CH potentiates respiratory, cardiovascular, and autonomic responses to peripheral chemoreceptor activation by hypoxia in patients with normal left ventricular function. The ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia, however, are significantly blunted.

Adult↗

Baseline blood pressure and other variables influencing survival on haemodialysis of patients without overt cardiovascular disease.

BACKGROUND: Age, diabetes and concomitant cardiovascular disease, recorded at the initiation of dialysis, allows the identification of patients with a high probability of early mortality. When all of these factors are taken into account the mortality rate of dialysis patients is still 3.5 times higher than for the general population. Information on the factors that increase the mortality of patients lacking the major cardiovascular risk factors is important because these are likely to be correctable, especially if detected early. METHODS: We investigated prospectively the relevance of blood pressure and other variables recorded at the initiation of dialysis treatment on the survival of a group of 103 relatively young adult haemodialysis patients (mean age 44.3 years +/-13 SD), with a low prevalence of comorbidity and a median follow-up period of 79 months. Data were analysed by the Cox proportional regression model and survival curves were constructed by the Kaplan-Meier method. RESULTS: Forty-four patients died, 20 (46%) of whom as a result of cardiovascular causes. Multivariate analysis showed that mortality was associated with age (P=0.0001), serum creatinine (P=0.005, negative association), left ventricular (LV) mass (P=0.003) and hypertension (P=0.03). Mortality was increased by 7% for each additional year of age, by 0.7% for each 1 g increase in LV mass, and was reduced by 23% for each additional mg/dl of serum creatinine. Hypertensive patients had a higher probability (x2.2) of dying compared with normotensive patients. CONCLUSIONS: In addition to age and conditions of occult malnutrition, hypertension and LV hypertrophy, when present at the initiation of dialysis, play a major role in the mortality of low risk, relatively young dialysis patients. These potentially correctable factors should be actively sought and treated during the early stage of renal insufficiency to improve prognosis.

Adult↗

Effects of exercise training on baroreflex control of the cardiovascular system.

Dynamic exercise training has been recommended as an antihypertensive therapy and as a way to modify the effects of many cardiovascular risk factors (Arakawa, 1993; Arroll and Beaglehole, 1992; Kelly and McClellan, 1994: see references 1-3 in the paper). However, the mechanisms underlying the blood-pressure lowering effect of chronic exercise are still poorly understood. It has been suggested that a decrease in sympathetic tone is one of the major effects elicited by chronic exercise on the cardiovascular system. The importance of the sympathetic component is confirmed in this review, since it was found that in spontaneously hypertensive rats (SHR) a marked decrease in sympathetic activity occurred after exercise training. Moreover, our findings suggest that this effect is mediated by improving the depressed baroreceptor function, which is, in part, responsible for the attenuation of the baroreflex sensitivity observed in the sedentary SHR (Krieger et al., 1998, 1999; see references 4 and 5 in the paper).

Animals↗

Abnormal neurovascular control during exercise is linked to heart failure severity.

The purpose of this study was to determine if abnormalities of sympathetic neural and vascular control are present in mild and/or severe heart failure (HF) and to determine the underlying afferent mechanisms. Patients with severe HF, mild HF, and age-matched controls were studied. Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) in the nonexercising arm were measured during mild and moderate static handgrip. MSNA during moderate handgrip was higher at baseline and throughout exercise in severe HF vs. mild HF (peak MSNA 67 +/- 3 vs. 54 +/- 3 bursts/min, P < 0.0001) and higher in mild HF vs. controls (33 +/- 3 bursts/min, P < 0.0001), but the change in MSNA was not different between the groups. The change in FVR was not significantly different between the three groups during static exercise. During isolation of muscle metaboreceptors, MSNA and blood pressure remained elevated in normal controls and mild HF but not in severe HF. During mild handgrip, the increase in MSNA was exaggerated in severe HF vs. controls and mild HF, in whom MSNA did not increase. In summary, the increase in MSNA during static exercise in severe HF appears to be attributable to exaggerated central command or muscle mechanoreceptor control, not muscle metaboreceptor control.

Adult↗

Baroreflex depression persists in the early phase after hypertension reversal.

The baroreflex control of heart rate (HR) was evaluated in conscious chronic renal hypertensive rats (RHR; 1K-1C, 2 mo) under control conditions and after reversal of hypertension by unclipping the renal artery or sodium nitroprusside infusion. Unclipping and nitroprusside infusion were both followed by significant decreases in the mean arterial pressure (unclipping: from 199 +/- 4 to 153 +/- 8 mmHg; nitroprusside infusion: from 197 +/- 9 to 166 +/- 6 mmHg) as well as slight and significant increases, respectively, in the baroreflex bradycardic response index (unclipping: from 0.2 +/- 0.04 to 0.6 +/- 0.1 beats x min(-1) x mmHg(-1); nitroprusside infusion: from 0.1 +/- 0.04 to 0.5 +/- 0.1 beats x min(-1) x mmHg(-1)). However, this index was still depressed compared with that for normotensive control rats (2.1 +/- 0.2 beats x min(-1) x mmHg(-1)). The index for the baroreflex tachycardic response was also depressed under control conditions and remained unchanged after hypertension reversal. RHR possessed markedly attenuated vagal tone as demonstrated by pharmacological blockade of parasympathetic and sympathetic control of HR with methylatropine and propranolol, respectively. A reduced bradycardic response was also observed in anesthetized RHR during electrical stimulation of the vagus nerve or methacholine chloride injection, indicating impairment of efferent vagal influence over the HR. Together, these data indicate that 2 h after hypertension reversal in RHR, the previously described normalization of baroreceptor gain occurs independent of the minimal or lack of recovery of baroreflex control over HR.

Animals↗

Hemodynamic and metabolic profile in offspring of malignant hypertensive parents.

Malignant hypertension is a serious form of arterial hypertension in which the physiopathological mechanisms include increased activity of the sympathetic nervous system, renin angiotensin system, and endothelium dysfunction. Family history of hypertension is an important predictive factor for hypertension and is associated with metabolic and hemodynamic abnormalities. Studies of these abnormalities in malignant hypertensive offspring have not yet been published. Therefore, we studied 42 offspring of malignant hypertensive parents (OMH group: age, 22+/-7 years; 23 male subjects; 27 white) and 35 offspring of normotensive parents (ONT group: age, 21+/-4 years; 23 male subjects; 25 white). All subjects had blood pressure <140/90 mm Hg. We evaluated body mass index; office blood pressure; 24-hour ambulatory and continuous beat-to-beat blood pressure monitoring (Finapres); biochemical analysis, including total cholesterol and fractions, triglycerides, glucose, and insulin; and hormonal analysis, including plasma renin activity, aldosterone, and catecholamines. The subjects were also submitted to cold pressure test and handgrip measurements. The body mass index was significantly higher in the OMH group (24+/-5 kg/m(2)) than in the ONT group (22+/-4 kg/m(2)). The OMH group showed significantly higher blood pressure and heart rate in office and Finapres measurements (P<0.05). In 24-hour ambulatory monitoring, the OMH group presented higher 24-hour blood pressure and heart rate, higher blood pressure during the night, and higher heart rate variability during the day compared with those of the ONT group. They also presented lower HDL cholesterol, higher levels of plasma insulin and norepinephrine, and higher insulin-to-glucose ratio (P<0.05) than the ONT group. There were no differences in the other biochemical parameters measured. In conclusion, OMH subjects show early hemodynamic, neurohumoral, and metabolic alterations that are typical of hypertensive metabolic syndrome.

Adolescent↗

Chronic AT(1) receptor blockade alters autonomic balance and sympathetic responses in hypertension.

In the coarctation hypertension model, we have shown that chronic treatment with losartan causes both normalization of impaired reflex control of heart rate and partial correction of the depressed aortic nerve activity/pressure relationship, even with the persistence of hypertension. In the present study, we analyzed the effects of angiotensin II blockade on the efferent pathways of coarcted and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day PO). Hypertension was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 9 days (4 control and 5 experimental days). On day 5, autoregressive power spectral analysis was performed on heart rate recordings made in conscious rats. Other groups were used for sympathetic splanchnic nerve activity recordings made simultaneously with pressure (anesthetized rats) at basal condition and during loading/unloading of baroreceptors. Losartan treatment induced a significant reduction in basal pressure but did not interfere with the development of hypertension (similar pressure increases of 24% and 28% over control values in losartan and vehicle groups, respectively). In vehicle-treated rats, establishment of hypertension was accompanied by a marked change in power spectral density from high- (1.19+/-0.06 Hz, 33+/-6%) to low-frequency components (0,42+/-0.03 Hz, 54+/-6%), with increased low-frequency-to-high-frequency ratio. When compared with sham-operated vehicle-treated rats, there was also increase in the gain of sympathetic activity/pressure relationship, with displacement of lower plateau toward high levels of sympathetic activity. No changes in the power spectral density and sympathetic activity/pressure relationship were observed when hypertension developed in the presence of chronic angiotensin type 1 (AT(1)) receptor blockade. The data suggest that angiotensin II, activated during the establishment of coarctation hypertension, acts via AT(1) receptors to alter sympathovagal balance, facilitating the sympathetic outflow to heart and peripheral circulation during baroreceptors unloading. Data also indicate that the observed effects are not conditioned by preexisting pressure levels.

Angiotensin Receptor Antagonists↗

Aging and baroreflex control of RSNA and heart rate in rats.

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 +/- 5 vs. 410 +/- 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 +/- 3 vs. 113 +/- 5 mmHg) or HR (344 +/- 9 vs. 347 +/- 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (-0.63 +/- 0. 18 vs. -1.84 +/- 0.4 bars x cycle(-1) x mmHg(-1) x s(-1)). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.

Aging↗

Exercise training increases baroreceptor gain sensitivity in normal and hypertensive rats.

Exercise training attenuates arterial hypertension and increases baroreflex sensitivity in spontaneous hypertension. However, no information exists regarding the portion of the baroreflex arch in which this attenuation takes place. We tested the hypothesis that exercise training increases the afferent pathway sensitivity of baroreflex control in both normotensive and spontaneously hypertensive rats (SHR). Arterial pressure and whole-nerve activity of the aortic baroreceptor (multifiber preparation) were evaluated in 30 male rats assigned to 4 groups: sedentary and exercise-trained normotensive rats and sedentary and exercise-trained SHR. Exercise training was performed on a motor treadmill, 5 d/wk for 60 minutes, gradually progressing toward a speed of 26.8 m/min. Exercise training reduced mean arterial pressure in conscious exercise-trained SHR (183+/-4 versus 165+/-7 mm Hg). The relation between changes in aortic baroreceptor discharge and changes in systolic arterial pressure increased significantly in exercise-trained normotensive rats (2.09+/-0.1 versus 1.44+/-0.1%/mm Hg) and exercise-trained SHR (0.92+/-0.1 versus 0.71+/-0.1%/mm Hg) compared with their respective sedentary rats. Likewise, the average aortic baroreceptor gain sensitivity (calculated by logistic equation) was significantly higher in exercise-trained normotensive rats (2.25+/-0.19 versus 1.77+/-0.03%/mm Hg) and exercise-trained SHR (1.07+/-0.04 versus 0.82+/-0.05%/mm Hg) compared with their respective sedentary control rats. In conclusion, exercise training increases aortic baroreceptor gain sensitivity in normotensive and SHR, thus improving baroreceptor sensitivity, which may result in a more efficient arterial pressure regulation by the baroreflexes.

Afferent Pathways↗

Decreased cardiopulmonary baroreflex sensitivity in Chagas' heart disease.

No study has been performed on reflexes originating from receptors in the heart that might be involved in the pathological lesions of Chagas' heart disease. Our study was undertaken to analyze the role of cardiopulmonary reflex on cardiovascular control in Chagas' disease. We studied 14 patients with Chagas' disease without heart failure and 12 healthy matched volunteers. Central venous pressure, arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were recorded during deactivation of cardiopulmonary receptors. By reducing central venous pressure by applying -10 and -15 mm Hg of negative pressure to the lower body, we observed (a) a similar decrease of central venous pressure in both groups; (b) a marked increase in forearm vascular resistance in the control group but a blunted increase in the Chagas' group; and (c) no significant changes in blood pressure and heart rate. To analyze cardiopulmonary and arterial receptors, we applied -40 mm Hg of lower-body negative pressure. As a consequence, (a) central venous pressure decreased similarly in both groups; (b) blood pressure was maintained in the control group, whereas in patients with Chagas' disease, a decrease in systolic and mean arterial pressure occurred; (c) heart rate increased in both groups; and (d) forearm vascular resistance increased significantly and similarly in both groups. Unloading of receptors with low levels of lower-body negative pressure did not increase forearm vascular resistance in patients with Chagas' disease, which suggests that the reflex mediated by cardiopulmonary receptors is impaired in patients with Chagas' disease without heart failure. Overall control of circulation appears to be compromised because patients did not maintain blood pressure under high levels of lower-body negative pressure.

Adult↗

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents.

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 +/- 11.7/78.5 +/- 8.6 mmHg, 137.3 +/- 12.3/74.4 +/- 7.9 mmHg, 68.5 +/- 8.4 bpm) compared to the FH- group (112.9 +/- 11.4/71.2 +/- 8.3 mmHg, 128.0 +/- 11. 8/66.5 +/- 7.4 mmHg, 62.1 +/- 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 +/- 104.5 pg/ml) than in the FH- group (169.1 +/- 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 +/- 0.3 vs 1.0 +/- 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group.

Adolescent↗

Acute AT1 receptor blockade does not improve the depressed baroreflex in rats with chronic renal hypertension.

To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 +/- 6 mmHg) than in normotensive rats (110 +/- 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16%), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (approximately 70% and approximately 65%, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level.

Angiotensin II↗

Blood pressure and the risk of complex arrhythmia in renal insufficiency, hemodialysis, and renal transplant patients.

Complex arrhythmia is frequent in hemodialysis patients but it is not clear if this is a consequence of dialysis or uremia or is secondary to the hemodynamic and cardiovascular alterations often associated with chronic renal failure. The incidence of complex ventricular arrhythmia (frequent multiform premature beats, couplets, and runs) in 31 subjects who had their uremic status recently corrected by renal transplant (Group 1) and in 23 predialysis (Group 2) and 73 hemodialysis (Group 3) chronic renal failure patients were studied with 24-h Holter monitoring. Patients were not receiving antiarrhythmic drugs or digitalis and significant coronary artery disease was excluded by clinical and noninvasive methods. Complex arrhythmia was two times more frequent in dialysis patients but the difference did not reach statistical significance (Group 1: 16%; Group 2: 17%; Group 3: 34%; chi2 4.9, P = .086). The stepwise model of logistic regression analysis identified systolic blood pressure (odds ratio 1.015, 95% confidence interval [CI] 1.001-1.027, P = .03) and left ventricular systolic dysfunction (odds ratio 7.04, 95% CI 1.3-36.7, P = .02) as the only factors that independently influenced the probability of complex arrhythmia. Age, gender, race, diabetes, smoking status, body mass index, diastolic blood pressure, serum creatinine, hematocrit, left ventricular mass index, and use of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatolytics, and calcium channel blockers did not influence the occurrence of complex arrhythmia. The data indicate that blood pressure and myocardial dysfunction are more important determinants of complex arrhythmia than dialysis or uremia in chronic renal disease patients.

Adult↗