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A new approach in the treatment of disabling orthostatic intolerance
POSTERS: Neural Mechanisms and Transmitters
E001 A FAMILY HISTORY OF OBESITY, A FAMILY HISTORY OF HYPERTENSION AND BLOOD PRESSURE LEVELS K. Masuo*, H. Mikami*, T. Ogihara*, and M.L. Tuck*. Osaka University Medical School, Suita City, Japan, and Sepulveda VA Medical Center, Sepulveda, CA We previously reported that family history (FH) of hypertension (HT) related with stimulated sympathetic activity and BP elevation in nonobese men over 10 years. In addition, it is probable the sympathetic nervous activation with weight gain is a major mechanism of blood pressure elevation. Hyperinsulinemia and hyperleptinemia may be ancillary factors, contributing to sympathetic nervous stimulation with weight. In the present study, we tried to delineate the effects of both family history of obesity (OBFH) and hypertension (HTFH) on BP levels in young men. A positive or a negative OBFH was defined as both parents were obese (BMI ⬎ 26.0 kg/m2) or lean (⬍ 22.0 kg/m2). A positive or a negative HTFH were defined as both parents were HT (⬎140/90 mmHg) or NT (⬉130/85 mmHg). The subjects were 21 lean OBFH⫺ & HTFH⫺, 7 lean OBFH⫺ & HTFH⫹, 8 lean OBFH⫹ & HTFH⫺, 5 lean OBFH⫹ & HTFH⫹, 9 obese OBFH⫺ & HTFH⫺, 5 obese OBFH⫺ & HTFH⫹, 16 obese OBFH⫹ & HTFH⫺, 17 obese OBFH⫹ & HTFH⫹. They were measured BMI, BP, pulse rate, plasma norepinephrine (NE), insulin, and leptin after overnight fast in supine position. The subjects were men and non-diabetic. Obese subjects had significantly higher levels in BP, NE and insulin than lean subjects regardless of OBFH or HTFH. In OBFH⫹ regardless of BMI, BP, NE, insulin, and leptin in HTFH⫹ were higher compared with HTFH⫺. On the other hand, in OBFH⫺, BP and NE in HTFH⫹ were higher than HTFH⫺, although plasma insulin and leptin in HTFH⫹ were similar to those in HTFH⫺. These results demonstrated that OBFH and HTFH contribute BP levels. Sympathetic activation with HTFH is a dominant mechanism in BP elevation, and hyperinsulinemia and hyperleptinemia may be ancillary factors with sympathetic activation in obese subjects and subjects with OBFH. Key Words: Sympathetic activity; leptin; obesity; family history of obesity; family history of hypertension E002 A NEW APPROACH IN THE TREATMENT OF DISABLING ORTHOSTATIC INTOLERANCE J. Freitas, R.M. Santos, E. Azevedo, O. Costa, M. Carvalho, and A. Falca˜o de Freitas. Centro de Estudos da Func¸a˜o Autono´mica—Hospital Sa˜o Joa˜o—Porto, Portugal Introduction: Orthostatic intolerance (OI) is a frequent misdiagnosis disabling condition. Objective: To evaluate the efficacy of drugs in the treatment of the autonomic/hemodynamic and clinical disturbance that characterizes OI patients. Material and Methods: 10 women, with a mean age 31 years (21 to 57 years), with orthostatic grade by symptoms ⱖ 3 © 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
AJH
2000;13:164A–168A
(florid POTS), were evaluated before (b) and after treatment (a). Five received oral bisoprolol (B) therapy, 2 pts flurocortisone (F) and 3 pts association of B and F. The patients were study in basal and tilt position. HRV, SBPV and spontaneous baroreceptor gain were calculated by FFT and ␣ index. The hemodynamic data was assessed by modelflow-TNO® analysis. Results:
Basal (b) Basal (a) Tilt (b) Tilt (a)
SV
TPR
58.1 60.6 34.0 41.6
1409 1733 2284 2241
BR␣
HR
15.2 92.5 22.8 69.5 4.4 121.4 11.8 81.9
LFrr
HFrr
SBP
LFsb
41.3 40.1 55.8 51.1
45.8 50.9 18.0 35.1
115.5 101.2 136.1 110.6
2.4 3.5 23.1 7.4
Units: HR in bpm; SV in ml; HRV in nu; SBPV in mmHg2; BR in ms/mmHg; TPR in dyn.s.cm-5; SBP in mmHg.
Conclusion: 1–Bisoprolol and/or flurocortisone improve the clinical and autonomic/hemodynamic disturbance observed in POTS. 2–All medical personnel must be alert to the diagnosis of this disabling misdiagnosis syndrome with such an easy treatment and marked clinical improvement. Key Words: Orthostatic intolerance; sympathetic activity; beta-blockers E003 EFFECT OF MONO- AND BILATERAL NEPHRECTOMY ON EFFERENT SYMPATHETIC NERVE ACTIVITY TO THE KIDNEYS IN THE RAT G. Recordati, F. Zorzoli, and A. Zanchetti. Centro Fisiologia Clinica ed Ipertensione, Universita’ di Milano and Ospedale Maggiore, Milano, Italy The object of this study was to verify if the removal of one or of both normal kidneys is accompanied by alterations in the efferent sympathetic nerve activity to the kidneys (RSNA). RSNA, blood pressure (BP), heart rate (HR), rate of breathing (RB), and rectal temperature (T) were continuously monitored for five hours in three groups of pentobarbital anesthetized, spontaneously breathing Sprague-Dawley (250 – 300 g) rats: group 1 (n ⫽ 5), both kidneys intact; group 2 (n ⫽ 5) and 3 (n ⫽ 5), left kidney excised. In addition in group 3, after one hour of control recording, the right renal hylus was tied to produce a complete, reversible, ischemia of the right kidney (functional right nephrectomy: FRN). In group 3 the RSNA was recorded continuously for one hour before, during three hours of FRN and for one hour after. In group 1 and 2, while BP, HR and RB remained fairly constant, RSNA progressively increased from a control value of 22.3 ⫾ 2.1 and of 26.7 ⫾ 1.2 imp/sec at time 0 (mean ⫾ S.E.) to 122.9 ⫾ 13.6 and to 80.9 ⫾ 10.7 imp/sec at time 5 h respectively. In contrast in group 3 RSNA progressively declined during the three hours of FRN, from a control value of 39.1 ⫾ 3.1 at time 1 h (beginning of FRN), to 13.7 ⫾ 2.6 imp/sec at time 4 h (end of FRN period), while BP and HR did not exhibit any significant alterations. The reopening of the right renal hylus was followed by a hypertensive and tachycardic episode, (described in a separate 0895-7061/00/$20.00
E001 A FAMILY HISTORY OF OBESITY, A FAMILY HISTORY OF HYPERTENSION AND BLOOD PRESSURE LEVELS K. Masuo*, H. Mikami*, T. Ogihara*, and M.L. Tuck*. Osaka University Medical School, Suita City, Japan, and Sepulveda VA Medical Center, Sepulveda, CA We previously reported that family history (FH) of hypertension (HT) related with stimulated sympathetic activity and BP elevation in nonobese men over 10 years. In addition, it is probable the sympathetic nervous activation with weight gain is a major mechanism of blood pressure elevation. Hyperinsulinemia and hyperleptinemia may be ancillary factors, contributing to sympathetic nervous stimulation with weight. In the present study, we tried to delineate the effects of both family history of obesity (OBFH) and hypertension (HTFH) on BP levels in young men. A positive or a negative OBFH was defined as both parents were obese (BMI ⬎ 26.0 kg/m2) or lean (⬍ 22.0 kg/m2). A positive or a negative HTFH were defined as both parents were HT (⬎140/90 mmHg) or NT (⬉130/85 mmHg). The subjects were 21 lean OBFH⫺ & HTFH⫺, 7 lean OBFH⫺ & HTFH⫹, 8 lean OBFH⫹ & HTFH⫺, 5 lean OBFH⫹ & HTFH⫹, 9 obese OBFH⫺ & HTFH⫺, 5 obese OBFH⫺ & HTFH⫹, 16 obese OBFH⫹ & HTFH⫺, 17 obese OBFH⫹ & HTFH⫹. They were measured BMI, BP, pulse rate, plasma norepinephrine (NE), insulin, and leptin after overnight fast in supine position. The subjects were men and non-diabetic. Obese subjects had significantly higher levels in BP, NE and insulin than lean subjects regardless of OBFH or HTFH. In OBFH⫹ regardless of BMI, BP, NE, insulin, and leptin in HTFH⫹ were higher compared with HTFH⫺. On the other hand, in OBFH⫺, BP and NE in HTFH⫹ were higher than HTFH⫺, although plasma insulin and leptin in HTFH⫹ were similar to those in HTFH⫺. These results demonstrated that OBFH and HTFH contribute BP levels. Sympathetic activation with HTFH is a dominant mechanism in BP elevation, and hyperinsulinemia and hyperleptinemia may be ancillary factors with sympathetic activation in obese subjects and subjects with OBFH. Key Words: Sympathetic activity; leptin; obesity; family history of obesity; family history of hypertension E002 A NEW APPROACH IN THE TREATMENT OF DISABLING ORTHOSTATIC INTOLERANCE J. Freitas, R.M. Santos, E. Azevedo, O. Costa, M. Carvalho, and A. Falca˜o de Freitas. Centro de Estudos da Func¸a˜o Autono´mica—Hospital Sa˜o Joa˜o—Porto, Portugal Introduction: Orthostatic intolerance (OI) is a frequent misdiagnosis disabling condition. Objective: To evaluate the efficacy of drugs in the treatment of the autonomic/hemodynamic and clinical disturbance that characterizes OI patients. Material and Methods: 10 women, with a mean age 31 years (21 to 57 years), with orthostatic grade by symptoms ⱖ 3 © 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
AJH
2000;13:164A–168A
(florid POTS), were evaluated before (b) and after treatment (a). Five received oral bisoprolol (B) therapy, 2 pts flurocortisone (F) and 3 pts association of B and F. The patients were study in basal and tilt position. HRV, SBPV and spontaneous baroreceptor gain were calculated by FFT and ␣ index. The hemodynamic data was assessed by modelflow-TNO® analysis. Results:
Basal (b) Basal (a) Tilt (b) Tilt (a)
SV
TPR
58.1 60.6 34.0 41.6
1409 1733 2284 2241
BR␣
HR
15.2 92.5 22.8 69.5 4.4 121.4 11.8 81.9
LFrr
HFrr
SBP
LFsb
41.3 40.1 55.8 51.1
45.8 50.9 18.0 35.1
115.5 101.2 136.1 110.6
2.4 3.5 23.1 7.4
Units: HR in bpm; SV in ml; HRV in nu; SBPV in mmHg2; BR in ms/mmHg; TPR in dyn.s.cm-5; SBP in mmHg.
Conclusion: 1–Bisoprolol and/or flurocortisone improve the clinical and autonomic/hemodynamic disturbance observed in POTS. 2–All medical personnel must be alert to the diagnosis of this disabling misdiagnosis syndrome with such an easy treatment and marked clinical improvement. Key Words: Orthostatic intolerance; sympathetic activity; beta-blockers E003 EFFECT OF MONO- AND BILATERAL NEPHRECTOMY ON EFFERENT SYMPATHETIC NERVE ACTIVITY TO THE KIDNEYS IN THE RAT G. Recordati, F. Zorzoli, and A. Zanchetti. Centro Fisiologia Clinica ed Ipertensione, Universita’ di Milano and Ospedale Maggiore, Milano, Italy The object of this study was to verify if the removal of one or of both normal kidneys is accompanied by alterations in the efferent sympathetic nerve activity to the kidneys (RSNA). RSNA, blood pressure (BP), heart rate (HR), rate of breathing (RB), and rectal temperature (T) were continuously monitored for five hours in three groups of pentobarbital anesthetized, spontaneously breathing Sprague-Dawley (250 – 300 g) rats: group 1 (n ⫽ 5), both kidneys intact; group 2 (n ⫽ 5) and 3 (n ⫽ 5), left kidney excised. In addition in group 3, after one hour of control recording, the right renal hylus was tied to produce a complete, reversible, ischemia of the right kidney (functional right nephrectomy: FRN). In group 3 the RSNA was recorded continuously for one hour before, during three hours of FRN and for one hour after. In group 1 and 2, while BP, HR and RB remained fairly constant, RSNA progressively increased from a control value of 22.3 ⫾ 2.1 and of 26.7 ⫾ 1.2 imp/sec at time 0 (mean ⫾ S.E.) to 122.9 ⫾ 13.6 and to 80.9 ⫾ 10.7 imp/sec at time 5 h respectively. In contrast in group 3 RSNA progressively declined during the three hours of FRN, from a control value of 39.1 ⫾ 3.1 at time 1 h (beginning of FRN), to 13.7 ⫾ 2.6 imp/sec at time 4 h (end of FRN period), while BP and HR did not exhibit any significant alterations. The reopening of the right renal hylus was followed by a hypertensive and tachycardic episode, (described in a separate 0895-7061/00/$20.00