Circadian Rhythms of Epinephrine and Norepinephrine in Man*

Linsell, C.; Lightman, Stafford; Mullen, Paul E.; Brown, M. J.; Causon, R. C.

doi:10.1210/jcem-60-6-1210

Cited by 372 publications

(186 citation statements)

References 20 publications

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“…However, few studies have standardized behavioral and environmental factors across the day/night cycle, which is a requirement to separate endogenous circadian from behavioral/ environmental effects (e.g., induced by the daily rest/activity cycle). Linsell et al (26) had indirect evidence of a circadian rhythm in plasma epinephrine (but not norepinephrine) based on 24-h fluctuations in epinephrine that could not be fully explained by sleep and/or posture. No daily rhythm in plasma or urinary epinephrine was found in a study in which subjects remained supine, but sleep/wake, feeding, and lighting conditions were not strictly controlled (27).…”

Section: Discussionmentioning

confidence: 99%

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

Scheer

Evoniuk

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

269

248

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The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.

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Section: Discussionmentioning

confidence: 99%

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

Scheer

Evoniuk

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

269

248

View full text Add to dashboard Cite

show abstract

“…29 Besides the circadian blood pressure pattern, increasing numbers of studies indicate that cardiovascular events occur more frequently in the morning, and that this phenomenon may be related to the morning blood pressure surge. 30 An anti-hypertensive medication that reduces the morning blood pressure surge would be useful in the prevention of cardiovascular events in hypertensive patients. The present study, the first prospective randomized trial to focus on a fixed combination of two anti-hypertensive medicines, found that similar to the chronotherapy studies of single medications, administration of amlodipine complex at bedtime significantly minimizes the morning surge, lowers the nocturnal blood pressure, increases the diurnal/ nocturnal ratio of blood pressure and reduces the number of nondipper patients.…”

Section: Discussionmentioning

confidence: 99%

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing—a multicenter, open-label randomized study

et al. 2011

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Previous studies have demonstrated that individual anti-hypertension medications have different effects when administered in the morning vs. the evening. However, the impact of administration timing on fixed combinations of anti-hypertensive medications on blood pressure control is still unknown. In the present study, we examined the administration time-dependent effects of a fixed combination of amlodipine and diuretics (amlodipine complex) on blood pressure in hypertensive subjects. Eighty patients from Chongqing City were enrolled in this study. Subjects were randomly assigned to receive a single pill (amlodipine complex, each tablet containing amlodipine 5 mg and hydrochlorothiazide 25 mg), either in the morning (0800 hours, n¼40) or at bedtime (2200 hours, n¼40). Blood pressure was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 24 consecutive hours before and after the 12 weeks of treatment. Following treatment, the 24-h mean systolic and diastolic blood pressures were reduced significantly in both the morning and bedtime groups. However, the morning blood pressure surge was reduced to a greater degree in the bedtime group. In addition, the nocturnal blood pressure and the 24 h mean blood pressure were lower in the bedtime group. More patients converted from having a non-dipper to dipper blood pressure in the bedtime group. These findings confirm that amlodipine complexes have different efficiencies depending on treatment time. Administration of amlodipine complexes at bedtime could optimize the anti-hypertensive effect by augmenting blood pressure-lowering effects, increasing the diurnal/nocturnal ratio of blood pressure, normalizing the blood pressure pattern and minimizing the morning blood pressure surge.

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“…At present, the precise mechanisms by which morning hypertension occur are not fully understood. However, abnormalities such as an increase in sympathetic nerve activity (23), excessive activity of RAS (24), and a hypercoagulable and hypofibrinolytic state may be involved in the process (25). Recently, Kamoi et al demonstrated that elevations of HBP in the morning in patients with diabetes are strongly related to microvascular and macrovascular complications, especially nephropathy, suggesting that the control of HBP in the morning is crucial to prevent further progression of the kidney (12).…”

Section: Morning Hypertension and Organ Damagementioning

confidence: 99%

Morning Blood Pressure Predicts Hypertensive Organ Damage in Patients with Renal Diseases: Effect of Intensive Antihypertensive Therapy in Patients with Diabetic Nephropathy

et al. 2005

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Blood pressure (BP) measured at home early in the morning (HBP) has been recognized as a useful predictor for organ damage and has been viewed as an important therapeutic target in patients with hypertension. The present study was aimed to determine whether this notion holds true in patients with progressive renal disease.The study enrolled patients with mild to moderate renal impairment. They were all directed to record selfmeasured HBP to evaluate the adequacy of BP control. In addition to the conventional antihypertensive therapy, intensive treatment to more efficiently reduce elevated morning HBP was applied, especially in patients with diabetic nephropathy. The results were as follows:1) The status of BP control assessed using HBP and office/clinic BP (OBP) shows predominance of morning hypertension. The prevalence of patients with well-controlled systolic HBP was 38%, those with poorly-controlled HBP 30%, masked hypertension 20% and white coat hypertension 12%. 2) Early morning systolic HBP in diabetics was significantly higher than that in non-diabetics. However, when evaluated on systolic OBP, both groups were comparable. 3) Logistic regression analysis showed that the predictive variables to explain morning hypertension (more than 130 mmHg and increased systolic HBP) were age, amount of daily urinary protein excretion and left ventricular mass index (LVMI). 4) Following conventional therapy, intensive antihypertensive therapy consisting of calcium channel blockers (CCB) and/or diuretics given in the morning, and angiotensin receptor blockers (ARB) given in the evening, together with 1-blockers given at bedtime, efficaciously reduced elevated HBP in the morning. This result was associated with significant reduction in daily urinary protein excretion and in serum plasminogen-activator inhibitor (PAI-1) concentration. The present study indicates that, regardless of ongoing conventional antihypertensive therapy, the majority of patients with renal disease had morning hypertension, suggesting that these patients are at a higher risk for cardiovascular disease. For the purpose of improving morning hypertension, intensive treatments with combined CCB, ARB and 1-blockers could have substantial benefit on the morbidity and prognosis in patients with diabetic nephropathy. (Internal Medicine 44: 1239-1246, 2005)

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Circadian Rhythms of Epinephrine and Norepinephrine in Man*

Cited by 372 publications

References 20 publications

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing—a multicenter, open-label randomized study

Morning Blood Pressure Predicts Hypertensive Organ Damage in Patients with Renal Diseases: Effect of Intensive Antihypertensive Therapy in Patients with Diabetic Nephropathy

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