Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension

Hashimoto, Junichiro; Chonan, Kenichi; Aoki, Y.; Ugajin, Tomohisa; Yamaguchi, Junko; Nishimura, Takuya; Kikuya, Masahiro; Michimata, Mari; Matsubara, Mitsunobu; Araki, Tsutomu; Hozawa, Atsushi; Ohkubo, Takayoshi; Imai, Yutaka

doi:10.1097/00004872-200304000-00025

Cited by 42 publications

(26 citation statements)

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“…The combination of drug-and gene-based therapies enables simultaneous treatment of all key metabolic syndrome pathologies. Guanabenz (Wytensin) is a clinically licensed antihypertensive drug that is thought to activate alpha-2-selective adrenergic receptors in the central nervous system, thereby reducing the sympathetic outflow to heart, kidney, and peripheral vasculature and decreasing the systolic and diastolic blood pressure (9). Recently, guanabenz was also identified as an agonist of the trace amine-associated receptor 1 (TAAR1) (10).…”

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confidence: 99%

Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome

Hamri

Zwicky

et al. 2012

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

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Synthetic biology has significantly advanced the design of genetic devices that can reprogram cellular activities and provide novel treatment strategies for future gene-and cell-based therapies. However, many metabolic disorders are functionally linked while developing distinct diseases that are difficult to treat using a classic one-drug-one-disease intervention scheme. For example, hypertension, hyperglycemia, obesity, and dyslipidemia are interdependent pathologies that are collectively known as the metabolic syndrome, the prime epidemic of the 21st century. We have designed a unique therapeutic strategy in which the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin. Therefore, the signal transduction of a chimeric traceamine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements. Based on this designer signaling cascade, it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc mIgG -Leptin, a bifunctional therapeutic peptide hormone that combines the glucagon-like peptide 1 (GLP-1) and leptin via an IgG-Fc linker. In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia. Using a clinically licensed drug to coordinate expression of therapeutic transgenes combines drug-and genebased therapies for coordinated treatment of functionally related metabolic disorders. T he metabolic syndrome is a combination of disorders and risk factors including hypertension, hyperglycemia, obesity, and dyslipidemia that show an extremely complex and littleunderstood interdependent pathophysiology and collectively increase the risk for cardiovascular diseases that remain the prime cause of mortality worldwide (1-8). Currently available therapies independently target each of the individual disorders and risk factors, but a well-coordinated collective treatment strategy does not exist (2). We have therefore designed a synthetic signaling cascade in which a clinically licensed small-molecule drug finetunes expression of therapeutic transgenes. The combination of drug-and gene-based therapies enables simultaneous treatment of all key metabolic syndrome pathologies. Guanabenz (Wytensin) is a clinically licensed antihypertensive drug that is thought to activate alpha-2-selective adrenergic receptors in the central nervous system, thereby reducing the sympathetic outflow to heart, kidney, and peripheral vasculature and decreasing the systolic and diastolic blood pressure (9). Recently, guanabenz was also identified as an agonist of the trace amine-associated receptor 1 (TAAR1) (10). TAARs are G protein-coupled receptors located in the neu...

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confidence: 99%

Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome

Hamri

Zwicky

et al. 2012

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

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“…58,59 It has recently been reported that the morning/evening (M/E) or evening/ morning (E/M) ratio obtained from home BP measurements is very effective in evaluating the duration of drug effects. 57,58,60 3) HOME BP AND TELEMEDICINE With the advance of devices for home BP measurements, BP values have begun to be stored as electronic data. As a result, such data have been transmitted via telephone lines or the internet, and are widely used for decision making [61][62][63][64][65] and clinical pharmacological evaluations.…”

Section: ) Home Bp and Prognosismentioning

confidence: 99%

“…Evaluating the trough effect allows a definition of the duration of action of the drugs. 60 Recently, morning hypertension has been attracting attention, and some antihypertensive drugs are administered just after waking to control morning hypertension. In such cases, BP measurements before drug ingestion are recommended, although measurements 5-10 min after drug ingestion are also permitted.…”

Section: Before Taking Antihypertensive Drugsmentioning

confidence: 99%

“…This concept is derived from the trough vs. peak (T/P) ratio obtained from ABPM. 59,60 To control hypertension in the morning, antihypertensive drugs have recently begun to be administered in the evening or just before bedtime. In this case, BP in the morning corresponds to near the peak effect and BP in the evening to near the trough effect.…”

Section: ) Measurement Procedures In the Eveningmentioning

confidence: 99%

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The Japanese Society of Hypertension Guidelines for Self-monitoring of Blood Pressure at Home (Second Edition)

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INTRODUCTIONSince Riva-Rocci invented indirect brachial cuff sphygmomanometry in 1896 1 and Korotkoff proposed the auscultatory method in 1905, 2 the method for blood pressure (BP) measurements has remained essentially unchanged for the past 100 years.In 1969, Posey et al. 3 identified mean BP on the basis of the cuff-oscillometric method. With subsequent theoretical and technical improvements, the method to determine systolic and diastolic BP (S and D, respectively) was introduced to the cuff-oscillometric method. As a result, many of the automatic electronic sphygmomanometers available today have adopted this method, and those different from the auscultatory method have begun to be used in general clinical practice. Since the advent of indirect methods for sphygmomanometry, the past century has developed the practical and clinical sciences of hypertension. However, BP information necessary for the diagnosis and treatment of hypertension is still obtained essentially on the basis of casual measurements at the outpatient clinic (clinic BP). However, the reliability of clinic BP was called into question 40 years after the advent of indirect sphygmomanometry. In 1940, Ayman and Goldshine 4 widely adopted the concept of self-BP measurements in the field of clinic BP measurements and demonstrated discrepancies between clinic BP and self-BP measurements. Bevan, 5 in the United Kingdom, first reported the results of ambulatory BP (ABP) monitoring (ABPM) using a direct arterial BP measurement method in 1969, and showed that human BP changes markedly with time. The quantity and quality of BP information vary greatly according to different methods, and the problem of interpreting clinic BP, which is obtained specifically in a medical environment, has been an issue in the clinical practice of hypertension during the past 50 years.However, the practice and epidemiology of hypertension still depend entirely on BP information obtained in a medical environment (clinic BP/BP at a health examination), resulting in the

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“…It has been demonstrated that treatment with sympatholytic drugs (eg, α-blockers, α, β-blockers, and central sympatholytic drugs) before bedtime is effective in the treatment of morning hypertension and morning surge. 54, 55 Bedtime administration of RA inhibitors is also used as a specific treatment of morning hypertension. It is expected that drugs inhibiting the RA system, which is activated at night and in the early morning, not only reduce blood pressure but also protect target organs.…”

Section: Morning Hypertensionmentioning

confidence: 99%

Guidelines for the Clinical Use of 24 Hour Ambulatory Blood Pressure Monitoring (ABPM) (JCS 2010) - Digest Version -

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Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension

Abstract: The results suggest that evening administration of the central alpha(2)-agonists guanabenz and clonidine effectively suppresses the morning BP elevation in treated hypertensive patients.

Cited by 42 publications

References 35 publications

Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome

Pharmaceutically controlled designer circuit for the treatment of the metabolic syndrome

The Japanese Society of Hypertension Guidelines for Self-monitoring of Blood Pressure at Home (Second Edition)

Guidelines for the Clinical Use of 24 Hour Ambulatory Blood Pressure Monitoring (ABPM) (JCS 2010) - Digest Version -

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