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Changes in autonomic tone during the time course of obesity induced hypertension in adolescents
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
circadian variation of BP, even though the level of BP did not change after LC lesion. Key Words: Spontaneously hypertensive rat (SHR); ultradian rhythm; locus coeruleus E009 ALPHA2-ADRENOCEPTOR CHARACTERISTICS IN SALT-SENSITIVE ESSENTIAL HYPERTENSIVE PATIENTS (EHT) A. Cases, S. Lario, V. Giner, M. Vera, A. de la Sierra, and A. Coca*. Hypertension Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain Salt-sensitivity in EHT has been reported to be related to an increased sympathetic drive. Previous studies have reported an increased platelet ␣2A-adrenoceptor (␣2A-ADR) density in a subset of patients with EHT. We hypothetized that an increased renal sodium reabsorption in salt-sensitive (SS) EHT patients may be related to an increased renal expression and/or function of ␣2A-ADR. With this aim we measured ␣2A-ADR in platelets of SS or salt-resistant (SR) EHT patients. We included 23 essential hypertensive patients (8 saltsensitive patients, 5M:3W, mean age 50.5 ⫾ 7.8 years; 15 salt-resistant patients 9M:6W, mean age 53.2 ⫾ 9.6 years). Salt-sensitivity was defined as a significant increase in 24-h mean arterial pressure after shifting from a low-sodium (50 mmol/d) to a high-sodium (250 mmol/d) diet for 1 week each. Platelet ␣2A-ADR characteristics were measured by radioligandbinding assay in intact cells using [3H]-methylyohimbine. There were no differences between the two groups with respect to age, sex, body mass index, mean arterial pressure or heart rate. Platelet ␣2A-ADR density (SS 167.8 ⫾ 48.1 vs SR 170.7 ⫾ 38.3 receptors/cell, mean ⫾ SD) and affinity (SS 1.2 ⫾ 0.3 vs SR 1.4 ⫾ 0.3 nM) were similar in the two groups of patients. These results suggest that salt-sensitivity in EHT is not due to an increased ␣2A-ADR density and/or affinity. Key Words: ␣2A-adrenoceptor; salt-sensitivity; essential hypertension E010 AUTONOMIC NERVOUS PATTERN IN MILD UNTREATED HYPERTENSIVE SUBJECTS: A FURTHER COMPONENT OF STRATIFICATION G. Cat Genova, T. Grosso, F. Rabbia, G. Martini, A. Conterno, A. Milan, C. Paglieri, and F. Veglio. Hypertension Unit, Department of Medicine and Experimental Oncology, Univesity of Turin, Italy Objective: Aim of this study was to assess autonomic nervous pattern in mild hypertensive patients, by analyzing time and frequency domain measures of heart rate variability (HRV) and evaluating baroreflex sensitivity (BRS). Methods: 86 essential never treated hypertensive patients (61/25 m/f, age 38 ⫾ 9 years, BMI 25.6 ⫾ 3.6, BP mean 150 ⫾ 14/97 ⫾ 8 mmHg, HR mean 80 ⫾ 12 bpm) underwent simultaneous 24-h Holter ecg and ambulatory BP monitoring. Power spectral analysis, performed by Fast Fourier
POSTERS: Neural Mechanisms and Transmitters
167A
transformation was used to assess autonomic control. The power was quantified in total spectral power, low frequency power (LF) and high frequency power (HF). In order to evaluate total and long term HRV, time domain parameters were calculated on the entire recording period: SDNN and SDANN as total and long term HRV indexes, RMSSD as index of vagal tone. In the same subjects noninvasive baroreceptor sensitivity (BRS) was estimated by Portapres device, using sequences technique. Results: Means values of BRs and RMSSD were 13.3 ⫾ 4.7 msec/mmHg and 31.2 ⫾ 11.5 msec, respectively. Subjects were stratified by tertile of BRS and RMSSD. SDNN, SDANN and RMSSD were significantly reduced in subjects in the lower tertile of BRS compared to those in the higher tertile. BRS and total short term variability of HR evaluated in frequency domain were significantly lower in the first than in the third tertile of RMSSD. Subjects with concurrent lower BRS and RMSSD (n ⫽ 15), despite similar clinical BP and HR values compared to subjects with higher BRS and RMSSD (n ⫽ 14), showed a significant increase of HR 24 h (79 ⫾ 2 vs 71 ⫾ 8 bpm, p ⫽ 0.02), both in day time and in night time. In the same group of subjects LFHF ratio, index of sympatho-vagal balance, was significantly higher (5.1 ⫾ 2.2 vs 3.3 ⫾ 0.6, p ⫽ 0.01). Conclusions: Among untreated hypertensives with similar clinical BP, HR values and anthropometric parameters, it is possible identify subsets of patients with different autonomic characteristics. The autonomic pattern may provide a further component for patients stratification, helping the first therapeutic decision. Key Words: Heart rate variability; baroreflex; autonomic nervous system; essential hypertension E011 CHANGES IN AUTONOMIC TONE DURING THE TIME COURSE OF OBESITY INDUCED HYPERTENSION IN ADOLESCENTS F. Rabbia, G. Martini, P. Riva, A. Milan, C. Paglieri, A. Conterno, G.B. Ferrero, V. Molini, and F. Veglio. Hypertension Unit, Dept. of Medicine and Experimental Oncology, University of Turin, Italy It has been proposed that obesity is associated with higher levels of sympathetic drive, however this is debated. Aim of the study was to assess cardiac autonomic control during the time course of pediatric obesity, by analysing time and frequency domain measures of heart period variability by 24-h Holter recording. 26 non-diabetic obese children (13.9 ⫾ 1.7 years old, BMI ⱖ 27) of and 14 sex, age-matched healthy lean subjects (12.9 ⫾ 1.6 ys) were studied. Obese children were grouped in recent obesity (ROB) (⬍6 years) and long term obesity (OB) (ⱖ6 years). In all participants, we performed anthropometric and blood pressure measures and a simultaneous, 24-h Holter ecg and ambulatory blood pressure monitoring (ABPM). 12-h fasting laboratory tests (i.e. glucose, insulin, total, HDL, LDL cholesterol, and triglycerides) were conducted. Power spectral analysis, performed by Fast Fourier transformation was used to assess autonomic control. The power was quantified in total spectral power (TP); low frequency power (LF), high frequency
168A
ASH XV ABSTRACTS
power (HF), LF and HF were averaged to obtain day-time and night-time levels. In order to evaluate total and long term HRV, TD parameters were calculated on the entire recording period. Both OB and ROB had higher casual blood pressure as compared to lean controls. In all considered time periods, time and frequency domain measures of overall variability were both significantly lower in the ROB group. This group of children had significantly higher 24-h and day-time low frequency normalized units. HF component showed an inverse but not significant pattern and 24-hour, day-time and night-time LF/HF ratio was significantly greater. Time domain measures of vagal activity were significantly decreased in the obese group, particularly in RO. We found sympathetic activation in the early phase of obesity, suggesting that autonomic nervous changes are dependent on the time course of obesity. Key Words: Obesity; heart rate variability; sympathetic tone; adolescents E012 ␣1-ADRENERGIC RECEPTOR SUBTYPES IN CIRCULATING MONONUCLEAR CELLS OF ESSENTIAL HYPERTENSIVES F. Veglio, D. Schiavone, A. Ricci, F. Rabbia, C. Paglieri, A. Milan, and F. Amenta. Hypertension Unit, Department of Medine and Experimental Oncology, University of Turin, Italy The expression of ␣1-adrenergic receptor subtypes was investigated in peripheral blood lymphocytes of stage 1, stage 2 and stage 3 essential hypertensives compared with healthy subjects using reverse transcription (RT) polymerase chain reaction (PCR), and radioligand binding assay techniques
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
combined with antibody against the three subtypes of ␣1adrenergic receptors (␣1A, ␣1B and ␣1D). RT-PCR amplified in peripheral blood lymphocytes ␣1A adrenergic receptor 348 bp fragment, ␣1B adrenergic receptor 689 bp fragment and ␣1D adrenergic receptor 540 bp fragment. The pharmacological profile of [3H]-prazosin binding to human peripheral blood lymphocytes was consistent with the labelling of ␣1-adrenergic receptors. The density of peripheral blood lymphocytes [3H]-prazosin binding decreased in essential hypertensives patients parallel to blood pressure value augmentation (p ⬍ 0.05). A higher density [3H]-prazosin binding sites was found in healthy subjects when compared with essential hypertensives (p ⬍ 0.01). In essential hypertensives, the antibodies against ␣1B receptors subtype decreased to a different extent [3H]-prazosin binding and parallel to the stage of hypertension (p ⬍ 0.05). In stage 2 and stage 3 hypertensives the ␣1A and the ␣1D respectively were the receptor subtypes lesser represented. The decreased density of peripheral lymphocytes ␣1-adrenergic receptor subtypes in essential hypertension may represent a downregulation mechanism consequent to impaired regulation of sympathoadrenal tone. In view of the involvement of ␣1-adrenergic receptor in the regulation of cardiovascular homeostasis, ␣1-adrenergic receptor subtype expression in human peripheral blood lymphocytes may represent a marker of the status of ␣1-adrenergic receptors in essential hypertension or may be useful for monitoring responses of these receptors to drug treatment. Key Words: Hypertension; receptors alpha adrenergic; receptors subtypes; receptor antibodies
circadian variation of BP, even though the level of BP did not change after LC lesion. Key Words: Spontaneously hypertensive rat (SHR); ultradian rhythm; locus coeruleus E009 ALPHA2-ADRENOCEPTOR CHARACTERISTICS IN SALT-SENSITIVE ESSENTIAL HYPERTENSIVE PATIENTS (EHT) A. Cases, S. Lario, V. Giner, M. Vera, A. de la Sierra, and A. Coca*. Hypertension Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain Salt-sensitivity in EHT has been reported to be related to an increased sympathetic drive. Previous studies have reported an increased platelet ␣2A-adrenoceptor (␣2A-ADR) density in a subset of patients with EHT. We hypothetized that an increased renal sodium reabsorption in salt-sensitive (SS) EHT patients may be related to an increased renal expression and/or function of ␣2A-ADR. With this aim we measured ␣2A-ADR in platelets of SS or salt-resistant (SR) EHT patients. We included 23 essential hypertensive patients (8 saltsensitive patients, 5M:3W, mean age 50.5 ⫾ 7.8 years; 15 salt-resistant patients 9M:6W, mean age 53.2 ⫾ 9.6 years). Salt-sensitivity was defined as a significant increase in 24-h mean arterial pressure after shifting from a low-sodium (50 mmol/d) to a high-sodium (250 mmol/d) diet for 1 week each. Platelet ␣2A-ADR characteristics were measured by radioligandbinding assay in intact cells using [3H]-methylyohimbine. There were no differences between the two groups with respect to age, sex, body mass index, mean arterial pressure or heart rate. Platelet ␣2A-ADR density (SS 167.8 ⫾ 48.1 vs SR 170.7 ⫾ 38.3 receptors/cell, mean ⫾ SD) and affinity (SS 1.2 ⫾ 0.3 vs SR 1.4 ⫾ 0.3 nM) were similar in the two groups of patients. These results suggest that salt-sensitivity in EHT is not due to an increased ␣2A-ADR density and/or affinity. Key Words: ␣2A-adrenoceptor; salt-sensitivity; essential hypertension E010 AUTONOMIC NERVOUS PATTERN IN MILD UNTREATED HYPERTENSIVE SUBJECTS: A FURTHER COMPONENT OF STRATIFICATION G. Cat Genova, T. Grosso, F. Rabbia, G. Martini, A. Conterno, A. Milan, C. Paglieri, and F. Veglio. Hypertension Unit, Department of Medicine and Experimental Oncology, Univesity of Turin, Italy Objective: Aim of this study was to assess autonomic nervous pattern in mild hypertensive patients, by analyzing time and frequency domain measures of heart rate variability (HRV) and evaluating baroreflex sensitivity (BRS). Methods: 86 essential never treated hypertensive patients (61/25 m/f, age 38 ⫾ 9 years, BMI 25.6 ⫾ 3.6, BP mean 150 ⫾ 14/97 ⫾ 8 mmHg, HR mean 80 ⫾ 12 bpm) underwent simultaneous 24-h Holter ecg and ambulatory BP monitoring. Power spectral analysis, performed by Fast Fourier
POSTERS: Neural Mechanisms and Transmitters
167A
transformation was used to assess autonomic control. The power was quantified in total spectral power, low frequency power (LF) and high frequency power (HF). In order to evaluate total and long term HRV, time domain parameters were calculated on the entire recording period: SDNN and SDANN as total and long term HRV indexes, RMSSD as index of vagal tone. In the same subjects noninvasive baroreceptor sensitivity (BRS) was estimated by Portapres device, using sequences technique. Results: Means values of BRs and RMSSD were 13.3 ⫾ 4.7 msec/mmHg and 31.2 ⫾ 11.5 msec, respectively. Subjects were stratified by tertile of BRS and RMSSD. SDNN, SDANN and RMSSD were significantly reduced in subjects in the lower tertile of BRS compared to those in the higher tertile. BRS and total short term variability of HR evaluated in frequency domain were significantly lower in the first than in the third tertile of RMSSD. Subjects with concurrent lower BRS and RMSSD (n ⫽ 15), despite similar clinical BP and HR values compared to subjects with higher BRS and RMSSD (n ⫽ 14), showed a significant increase of HR 24 h (79 ⫾ 2 vs 71 ⫾ 8 bpm, p ⫽ 0.02), both in day time and in night time. In the same group of subjects LFHF ratio, index of sympatho-vagal balance, was significantly higher (5.1 ⫾ 2.2 vs 3.3 ⫾ 0.6, p ⫽ 0.01). Conclusions: Among untreated hypertensives with similar clinical BP, HR values and anthropometric parameters, it is possible identify subsets of patients with different autonomic characteristics. The autonomic pattern may provide a further component for patients stratification, helping the first therapeutic decision. Key Words: Heart rate variability; baroreflex; autonomic nervous system; essential hypertension E011 CHANGES IN AUTONOMIC TONE DURING THE TIME COURSE OF OBESITY INDUCED HYPERTENSION IN ADOLESCENTS F. Rabbia, G. Martini, P. Riva, A. Milan, C. Paglieri, A. Conterno, G.B. Ferrero, V. Molini, and F. Veglio. Hypertension Unit, Dept. of Medicine and Experimental Oncology, University of Turin, Italy It has been proposed that obesity is associated with higher levels of sympathetic drive, however this is debated. Aim of the study was to assess cardiac autonomic control during the time course of pediatric obesity, by analysing time and frequency domain measures of heart period variability by 24-h Holter recording. 26 non-diabetic obese children (13.9 ⫾ 1.7 years old, BMI ⱖ 27) of and 14 sex, age-matched healthy lean subjects (12.9 ⫾ 1.6 ys) were studied. Obese children were grouped in recent obesity (ROB) (⬍6 years) and long term obesity (OB) (ⱖ6 years). In all participants, we performed anthropometric and blood pressure measures and a simultaneous, 24-h Holter ecg and ambulatory blood pressure monitoring (ABPM). 12-h fasting laboratory tests (i.e. glucose, insulin, total, HDL, LDL cholesterol, and triglycerides) were conducted. Power spectral analysis, performed by Fast Fourier transformation was used to assess autonomic control. The power was quantified in total spectral power (TP); low frequency power (LF), high frequency
168A
ASH XV ABSTRACTS
power (HF), LF and HF were averaged to obtain day-time and night-time levels. In order to evaluate total and long term HRV, TD parameters were calculated on the entire recording period. Both OB and ROB had higher casual blood pressure as compared to lean controls. In all considered time periods, time and frequency domain measures of overall variability were both significantly lower in the ROB group. This group of children had significantly higher 24-h and day-time low frequency normalized units. HF component showed an inverse but not significant pattern and 24-hour, day-time and night-time LF/HF ratio was significantly greater. Time domain measures of vagal activity were significantly decreased in the obese group, particularly in RO. We found sympathetic activation in the early phase of obesity, suggesting that autonomic nervous changes are dependent on the time course of obesity. Key Words: Obesity; heart rate variability; sympathetic tone; adolescents E012 ␣1-ADRENERGIC RECEPTOR SUBTYPES IN CIRCULATING MONONUCLEAR CELLS OF ESSENTIAL HYPERTENSIVES F. Veglio, D. Schiavone, A. Ricci, F. Rabbia, C. Paglieri, A. Milan, and F. Amenta. Hypertension Unit, Department of Medine and Experimental Oncology, University of Turin, Italy The expression of ␣1-adrenergic receptor subtypes was investigated in peripheral blood lymphocytes of stage 1, stage 2 and stage 3 essential hypertensives compared with healthy subjects using reverse transcription (RT) polymerase chain reaction (PCR), and radioligand binding assay techniques
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
combined with antibody against the three subtypes of ␣1adrenergic receptors (␣1A, ␣1B and ␣1D). RT-PCR amplified in peripheral blood lymphocytes ␣1A adrenergic receptor 348 bp fragment, ␣1B adrenergic receptor 689 bp fragment and ␣1D adrenergic receptor 540 bp fragment. The pharmacological profile of [3H]-prazosin binding to human peripheral blood lymphocytes was consistent with the labelling of ␣1-adrenergic receptors. The density of peripheral blood lymphocytes [3H]-prazosin binding decreased in essential hypertensives patients parallel to blood pressure value augmentation (p ⬍ 0.05). A higher density [3H]-prazosin binding sites was found in healthy subjects when compared with essential hypertensives (p ⬍ 0.01). In essential hypertensives, the antibodies against ␣1B receptors subtype decreased to a different extent [3H]-prazosin binding and parallel to the stage of hypertension (p ⬍ 0.05). In stage 2 and stage 3 hypertensives the ␣1A and the ␣1D respectively were the receptor subtypes lesser represented. The decreased density of peripheral lymphocytes ␣1-adrenergic receptor subtypes in essential hypertension may represent a downregulation mechanism consequent to impaired regulation of sympathoadrenal tone. In view of the involvement of ␣1-adrenergic receptor in the regulation of cardiovascular homeostasis, ␣1-adrenergic receptor subtype expression in human peripheral blood lymphocytes may represent a marker of the status of ␣1-adrenergic receptors in essential hypertension or may be useful for monitoring responses of these receptors to drug treatment. Key Words: Hypertension; receptors alpha adrenergic; receptors subtypes; receptor antibodies