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Analysis of adenylate cyclase activity in Japanese children with orthostatic dysregulation
Nobuyoshi Sugiyama1,2, Tomoyoshi Komiyama3, Kengo Ayabe4,5
1Department of Pediatrics, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Insights
Increased adenylate cyclase activity may cause orthostatic dysregulation in children. This study found higher enzyme levels in patients with postural orthostatic tachycardia syndrome and delayed orthostatic hypotension, suggesting a diagnostic role.
Area of Science:
- Cardiovascular Physiology
- Pediatric Endocrinology
Background:
- Orthostatic dysregulation, including postural orthostatic tachycardia syndrome (POTS) and delayed orthostatic hypotension (DOH), affects children.
- The precise etiology of these conditions remains unclear.
Purpose of the Study:
- To investigate the role of adenylate cyclase activity in the pathogenesis of orthostatic dysregulation in Japanese children.
- To explore potential diagnostic biomarkers for orthostatic dysregulation.
Main Methods:
- Measured resting blood adenylate cyclase activity (using isoproterenol and adrenaline) in 30 pediatric patients with orthostatic dysregulation (21 POTS, 8 DOH, 1 immediate OH) and 20 healthy controls.
- Analyzed basic clinical data including blood pressure and pulse rate.
Main Results:
- Significantly higher adenylate cyclase activity was observed in patients with POTS compared to DOH and healthy adults across all tested concentrations.
- Patients with POTS exhibited higher systolic blood pressure than those with DOH.
- A trend towards increased adenylate cyclase activity was noted in DOH patients at a specific adrenaline concentration.
Conclusions:
- Elevated adenylate cyclase activity is strongly associated with POTS and may contribute to the pathophysiology of orthostatic dysregulation.
- Adenylate cyclase activity levels present a potential new diagnostic strategy for identifying and differentiating types of orthostatic dysregulation.
Abstract:
The aim of the study was to clarify the cause of orthostatic dysregulation in Japanese children by analyzing fluctuations in adenylate cyclase activity. Four types of orthostatic dysregulation in Japan include postural orthostatic tachycardia syndrome, delayed orthostatic hypotension, immediate orthostatic hypotension, and vasovagal syncope. However, the exact cause of these disorders remains unknown. To identify the cause of these conditions, we examined the resting blood adenylate cyclase activity and basic clinical data (blood pressure, pulse rate) of 30 patients diagnosed with orthostatic dysregulation (21 postural orthostatic tachycardia syndrome, eight delayed orthostatic hypotension, one immediate orthostatic hypotension, zero vasovagal syncope) and 20 previously reported healthy adults. The results of this study showed that adenylate cyclase activity (isoproterenol and adrenaline) in patients with postural orthostatic tachycardia syndrome was significantly higher than that in patients with delayed orthostatic hypotension and healthy adults. Moreover, patients with postural orthostatic tachycardia syndrome had significantly higher values than healthy adult controls at all five concentration points. Adenylate cyclase activity in patients with delayed orthostatic hypotension showed a trend toward higher values at 10 μM of adrenaline. Furthermore, owing to the higher adenylate cyclase activity in patients with postural orthostatic tachycardia syndrome, their systolic blood pressure was higher than that in patients with delayed orthostatic hypotension. These results suggest that increased adenylate cyclase activity may be related to the onset of orthostatic dysregulation (postural orthostatic tachycardia syndrome and delayed orthostatic hypotension). In conclusion, adenylate cyclase activity levels may be related to the onset of orthostatic dysregulation, and this can be used as a new strategy for diagnosing orthostatic dysregulation.
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