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Increased cardiovascular responses to norepinephrine in patients with hypertrophic cardiomyopathy
1Third Department of Medicine, Kurume University School of Medicine, Japan.
Insights
Patients with hypertrophic cardiomyopathy (HCM) show heightened cardiovascular responses to norepinephrine (NE), suggesting increased adrenergic receptor activity, not enhanced sympathetic nerve function, may drive HCM development.
Area of Science:
- Cardiology
- Physiology
- Pharmacology
Background:
- Sympathetic nerve-adrenergic receptor systems are linked to hypertrophic cardiomyopathy (HCM) pathogenesis.
- Understanding the role of these systems is crucial for managing HCM.
Purpose of the Study:
- To investigate plasma norepinephrine levels during exercise in HCM patients.
- To assess cardiovascular responses to norepinephrine infusion in nonobstructive HCM patients compared to controls.
Main Methods:
- Studied 26 nonobstructive HCM patients and 26 matched controls.
- Measured plasma norepinephrine levels at rest and during exercise.
- Administered intravenous norepinephrine infusions to assess cardiovascular effects.
Main Results:
- No significant differences in resting or exercise-induced plasma norepinephrine levels were found.
- HCM patients exhibited significantly greater increases in blood pressure and peripheral vascular resistance upon norepinephrine infusion.
- Left ventricular contractility responses to norepinephrine were augmented in HCM patients, unlike controls.
Conclusions:
- Cardiovascular adrenergic receptor system activity is heightened in HCM patients.
- Enhanced sympathetic nervous function is unlikely to be the primary driver of abnormal hypertrophy in HCM.
- Findings suggest a potential therapeutic target in modulating adrenergic receptor activity in HCM.
Abstract:
Sympathetic nerve-adrenergic receptor systems have been implicated in the pathogenesis of hypertrophic cardiomyopathy (HCM). We studied plasma norepinephrine (NE) levels during exercise and cardiovascular responses to NE in 26 patients with nonobstructive HCM and 26 age- and sex-matched controls. There were no differences in the plasma NE levels at rest (201 +/- 84 vs 233 +/- 100 pg/ml) or in the slope of the log NE-heart rate relationship during exercise between the HCM patient and control groups. When NE was infused intravenously, with increasing doses to 0.20 microgram/kg/min, HCM patients displayed significantly greater increases in mean blood pressure (29 +/- 7 vs 14 +/- 5%, p less than 0.001) and peripheral vascular resistance (39 +/- 7 vs 26 +/- 7%, p less than 0.001) than controls. Although the fractional shortening decreased during NE infusion in controls, it was unaffected in HCM patients, despite a greater elevation of systolic pressure. The responses of left ventricular contractility, estimated by a ratio of systolic blood pressure to end-systolic dimension, were significantly greater in patients with HCM (31 +/- 7 vs 13 +/- 6%, p less than 0.001). These observations indicate that vasoconstrictive responses of the peripheral arteries and inotropic responses of the left ventricular muscle to NE were augmented in patients with HCM, while sympathetic nervous activity remained unchanged. Accordingly, we propose that increased activity of the cardiovascular adrenergic receptor systems, rather than enhanced sympathetic nervous function, may be related to the development of abnormal hypertrophy in HCM.