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Abnormal cardiovascular responses to tilt table testing in young healthy individuals with family history of hypertension
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
POSTERS: Neural Mechanisms and Transmitters
165A
communication), and by short lasting complex alterations of RSNA. These data show that the removal of both kidneys is accompanied by a clear progressive reduction in the RSNA, thus suggesting that the normal kidneys exert a supportive and facilitatory role on efferent sympathetic activity directed back to the kidneys either through a reflex mechanism initiated by afferent renal nerves or substances released from the kidneys.
E005 DIFFERENTIAL DISTRIBUTION OF G-PROTEINCOUPLED RECEPTOR KINASE TYPES 2, 3, 4, 5, AND 6 IN HUMAN BRAIN: AN IMMUNOHISTOCHEMICAL ANALYSIS H. Watanabe, M.A. Stier, H. Sanada, P.A. Jose, and R.A. Felder*. The University of Virginia, Department of Pathology, Charlottesville, VA, 22908. Georgetown University Hospital, Department of Pediatrics, Washington, D.C. 20007
Key Words: Nephrectomy; sympathetic nerve activity; renin-angiotensin system; renal sensory innervation
G protein-coupled receptor kinases (GRKs) inhibit the signaling pathways of G-protein related receptors through protein phosphorylation. GRKs have been shown to be involved in various neuronal signaling pathways. However, a systematic localization of GRK isoforms has not been demonstrated in the human central nervous system. We show immunohistochemical localization of GRK type 2– 6 in 5 um slices of fresh postmortem human brain fixed with Histochoice. GRK6 immunoreactivity was identified in neuronal cytoplasm, and dense fiber tracks in the basal ganglia. Dense staining was also noted in the media of varying caliber arterial blood vessels. Extensive GRK4 staining was noted. Therefore, we examined various GRK4 isoforms for their anatomical immunoreactive distribution. GRK4 alpha-beta (antisera cannot differentiate between the alpha and beta isoforms) was positive in fibers of the pontine reticular formation, substantia nigra, and basal ganglia. Astrocytic cell processes also appear distinctly positive for GRK4 alpha-beta. GRK gamma-delta showed distinct reactivity in fibers near the amygdaloid complex, neurons and fibers in the hippocampus and pontine reticular formation, and in the adventitia of arterial blood vessels. GRK4 theta-epsilon was positive in cellular processes and neurons in the hippocampus, ependema, leptomeninges, and all layers of arterial blood vessels. In our hands, we could not demonstrate immunostaining for GRK 2, 3 and 5 in human brain. Our results suggest that GRKs may have differential roles in the modulation of the central nervous system due to the wide variation in their anatomical distribution.
E004 ABNORMAL CARDIOVASCULAR RESPONSES TO TILT TABLE TESTING IN YOUNG HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF HYPERTENSION A. Babaev, N. Khamidov, and Kh. Rafiev. Tajik State Medical University, Dushanbe, Tajikistan The aim of the study was to evaluate the cardiovascular responses to head-upright tilt table test in young healthy subjects with and without family history of essential hypertension (HTN). We studied 56 young healthy males, who were divided into two groups: Group I–25 subjects with family history of HTN (one or both parents), and Group II–31 individuals without. Groups were comparable by age, blood pressure and body mass index (BMI) (Table 1). All subjects underwent 70 degrees head-upright tilt table testing of 10 minutes duration. Blood pressure and heart rate were constantly monitored during the test. All participants took no medications for at least 1 month, and no caffeinated beverages for 12 hours prior to the study.
Group I Group II P value
Age
BMI
SBP
DBP
HR
23 ⫾ 1.5 23 ⫾ 1.6 n.s.
23 ⫾ 1.5 23.3 ⫾ 1.6 n.s.
113 ⫾ 7.0 112 ⫾ 8.0 n.s.
72.9 ⫾ 6.2 71 ⫾ 6.3 n.s.
65 ⫾ 7 66 ⫾ 8 n.s.
There were no significant differences in systolic blood pressure and heart rate responses to head-upright tilt, but diastolic blood pressure rise was significantly greater in individuals with family history of hypertension (Table 2).
Group I Group II P value
⌬SBP mm Hg
⌬ DBP mm Hg
⌬ HR bpm
⫺2 ⫾ 4.9 ⫺.4 ⫾ 7.1 n.s.
4.2 ⫾ 4.1 11.4 ⫾ 3.9 P ⬍ 0.001
18.9 ⫾ 5.3 20 ⫾ 6.3 n.s.
Conclusion: Healthy young subjects with family history of hypertension have an exaggerated diastolic BP response to orthostasis. This finding is probably suggestive of hereditary abnormality in baroreflex mechanisms predisposing these individuals to the development of HTN. Key Words: Baroreflex; orthostasis
Key Words: G-protein related kinase; G-protein coupled receptor; human; brain; central nervous system E006 MORNING BLOOD PRESSURE SURGE DERIVES FROM CENTRAL SYMPATHETIC NERVE ACTIVITY BUT NOT FROM PARASYMPATHETIC ACTIVITY E. Miyajima, T. Shigemasa, Y. Kawano, T. Endo, and S. Umemura. Division of Cardiology, Yokohama City University, Medical Center, Yokohama, Japan Although cardiovascular events appears to be greatest in the early morning, blood pressure control in this period may not be sufficient by the first-line antihypertensive drugs. Since sympathetic nervous system may be responsible for this morning blood pressure surge, centrally acting ␣2 agonists may inhibit these responses. We examined ambulatory blood pressure (BP) and ECG for 24 hours in 101 hypertensive patients (54 ⫾ 1 y old; 68 men and 33 women). HF (0.15– 0.4 Hz) and LF/HF ratio of heart rate variability (HRV) were calculated by maximum entropy methods in each 2-min interval. The data used were 4 h before and 4 h
POSTERS: Neural Mechanisms and Transmitters
165A
communication), and by short lasting complex alterations of RSNA. These data show that the removal of both kidneys is accompanied by a clear progressive reduction in the RSNA, thus suggesting that the normal kidneys exert a supportive and facilitatory role on efferent sympathetic activity directed back to the kidneys either through a reflex mechanism initiated by afferent renal nerves or substances released from the kidneys.
E005 DIFFERENTIAL DISTRIBUTION OF G-PROTEINCOUPLED RECEPTOR KINASE TYPES 2, 3, 4, 5, AND 6 IN HUMAN BRAIN: AN IMMUNOHISTOCHEMICAL ANALYSIS H. Watanabe, M.A. Stier, H. Sanada, P.A. Jose, and R.A. Felder*. The University of Virginia, Department of Pathology, Charlottesville, VA, 22908. Georgetown University Hospital, Department of Pediatrics, Washington, D.C. 20007
Key Words: Nephrectomy; sympathetic nerve activity; renin-angiotensin system; renal sensory innervation
G protein-coupled receptor kinases (GRKs) inhibit the signaling pathways of G-protein related receptors through protein phosphorylation. GRKs have been shown to be involved in various neuronal signaling pathways. However, a systematic localization of GRK isoforms has not been demonstrated in the human central nervous system. We show immunohistochemical localization of GRK type 2– 6 in 5 um slices of fresh postmortem human brain fixed with Histochoice. GRK6 immunoreactivity was identified in neuronal cytoplasm, and dense fiber tracks in the basal ganglia. Dense staining was also noted in the media of varying caliber arterial blood vessels. Extensive GRK4 staining was noted. Therefore, we examined various GRK4 isoforms for their anatomical immunoreactive distribution. GRK4 alpha-beta (antisera cannot differentiate between the alpha and beta isoforms) was positive in fibers of the pontine reticular formation, substantia nigra, and basal ganglia. Astrocytic cell processes also appear distinctly positive for GRK4 alpha-beta. GRK gamma-delta showed distinct reactivity in fibers near the amygdaloid complex, neurons and fibers in the hippocampus and pontine reticular formation, and in the adventitia of arterial blood vessels. GRK4 theta-epsilon was positive in cellular processes and neurons in the hippocampus, ependema, leptomeninges, and all layers of arterial blood vessels. In our hands, we could not demonstrate immunostaining for GRK 2, 3 and 5 in human brain. Our results suggest that GRKs may have differential roles in the modulation of the central nervous system due to the wide variation in their anatomical distribution.
E004 ABNORMAL CARDIOVASCULAR RESPONSES TO TILT TABLE TESTING IN YOUNG HEALTHY INDIVIDUALS WITH FAMILY HISTORY OF HYPERTENSION A. Babaev, N. Khamidov, and Kh. Rafiev. Tajik State Medical University, Dushanbe, Tajikistan The aim of the study was to evaluate the cardiovascular responses to head-upright tilt table test in young healthy subjects with and without family history of essential hypertension (HTN). We studied 56 young healthy males, who were divided into two groups: Group I–25 subjects with family history of HTN (one or both parents), and Group II–31 individuals without. Groups were comparable by age, blood pressure and body mass index (BMI) (Table 1). All subjects underwent 70 degrees head-upright tilt table testing of 10 minutes duration. Blood pressure and heart rate were constantly monitored during the test. All participants took no medications for at least 1 month, and no caffeinated beverages for 12 hours prior to the study.
Group I Group II P value
Age
BMI
SBP
DBP
HR
23 ⫾ 1.5 23 ⫾ 1.6 n.s.
23 ⫾ 1.5 23.3 ⫾ 1.6 n.s.
113 ⫾ 7.0 112 ⫾ 8.0 n.s.
72.9 ⫾ 6.2 71 ⫾ 6.3 n.s.
65 ⫾ 7 66 ⫾ 8 n.s.
There were no significant differences in systolic blood pressure and heart rate responses to head-upright tilt, but diastolic blood pressure rise was significantly greater in individuals with family history of hypertension (Table 2).
Group I Group II P value
⌬SBP mm Hg
⌬ DBP mm Hg
⌬ HR bpm
⫺2 ⫾ 4.9 ⫺.4 ⫾ 7.1 n.s.
4.2 ⫾ 4.1 11.4 ⫾ 3.9 P ⬍ 0.001
18.9 ⫾ 5.3 20 ⫾ 6.3 n.s.
Conclusion: Healthy young subjects with family history of hypertension have an exaggerated diastolic BP response to orthostasis. This finding is probably suggestive of hereditary abnormality in baroreflex mechanisms predisposing these individuals to the development of HTN. Key Words: Baroreflex; orthostasis
Key Words: G-protein related kinase; G-protein coupled receptor; human; brain; central nervous system E006 MORNING BLOOD PRESSURE SURGE DERIVES FROM CENTRAL SYMPATHETIC NERVE ACTIVITY BUT NOT FROM PARASYMPATHETIC ACTIVITY E. Miyajima, T. Shigemasa, Y. Kawano, T. Endo, and S. Umemura. Division of Cardiology, Yokohama City University, Medical Center, Yokohama, Japan Although cardiovascular events appears to be greatest in the early morning, blood pressure control in this period may not be sufficient by the first-line antihypertensive drugs. Since sympathetic nervous system may be responsible for this morning blood pressure surge, centrally acting ␣2 agonists may inhibit these responses. We examined ambulatory blood pressure (BP) and ECG for 24 hours in 101 hypertensive patients (54 ⫾ 1 y old; 68 men and 33 women). HF (0.15– 0.4 Hz) and LF/HF ratio of heart rate variability (HRV) were calculated by maximum entropy methods in each 2-min interval. The data used were 4 h before and 4 h