Placebo-controlled Comparison of the Efficacy and Tolerability of Once-daily Moxonidine and Enalapril in Mild to Moderate Essential Hypertension

Prichard, B. N. C.; Jäger, Bodo; Luszick, Joachim; Küster, Leslie J.; Verboom, C.N.; Hughes, Peter R.; Sauermann, W; Küppers, H

doi:10.1080/080370502760050403

Cited by 19 publications

(16 citation statements)

References 20 publications

(22 reference statements)

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“…19 However, the use of centrally acting sympatholytics is nonspecific and limited by adverse effects, leading to high nonadherence rates. 20 Elevated fasting glucose levels, impaired glucose tolerance, and diabetes mellitus have been associated with an increased risk of cardiovascular disease [21][22][23][24] resulting from stimulation of inflammation, oxidative stress, and thrombotic activity, 25 as well as inhibition of vascular smooth muscle cell apoptosis. 26 Approximately 50% of patients with essential hypertension are considered to be insulin resistant.…”

Section: Discussionmentioning

confidence: 99%

Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension

et al. 2011

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Background-Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results-We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96Ϯ3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by Ϫ28/Ϫ10 mm Hg (PϽ0.001) and Ϫ32/Ϫ12 mm Hg (PϽ0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118Ϯ3.4 to 108Ϯ3.8 mg/dL (Pϭ0.039). Insulin levels were decreased from 20.8Ϯ3.0 to 9.3Ϯ2.5 IU/mL (Pϭ0.006) and C-peptide levels from 5.3Ϯ0.6 to 3.0Ϯ0.9 ng/mL (Pϭ0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0Ϯ0.9 to 2.4Ϯ0.8 (Pϭ0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (Pϭ0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions-Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.

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Section: Discussionmentioning

confidence: 99%

Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension

et al. 2011

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“…Tissot et al [19••] speculated that the modest renin response to angiotensin vaccination was due to the slow accumulation of angiotensin II antibodies, with a corresponding slow effect on free angiotensin II concentrations, in contrast to the abrupt effects of ACE inhibitor or ARB therapies. However, this speculation is based on the assumption that renin-angiotensin system blockade by angiotensin II vaccination was comparable to that produced by ACE inhibitor and ARB therapies, an assumption that is not supported by the much smaller reduction in blood pressure with angiotensin II vaccination than observed with ACE inhibitor or ARB therapy [28][29][30].…”

Section: Renin Response To Angiotensin Vaccinationmentioning

confidence: 93%

Angiotensin vaccination: What is the prospect of success?

Campbell

2009

Current Science Inc

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Over many decades, several attempts have been made to treat hypertension using a vaccination strategy to inhibit the renin-angiotensin system. Renin vaccination successfully inhibited renin activity and reduced blood pressure in animal models, but caused autoimmune disease of the kidney. By contrast, most previous studies of angiotensin vaccination failed to reduce blood pressure in animal models, despite producing high titers of antibodies that prevented the pressor response to exogenous angiotensins. Angiotensin vaccination is being revisited as a strategy for treating hypertension, in the hope that new conjugates of angiotensin I and angiotensin II will produce antibodies of sufficient titer and affinity to reduce blood pressure in patients with hypertension. A recent clinical study of angiotensin II vaccination provided some cause for optimism, but many hurdles remain before this strategy can compete with current oral medications for hypertension.

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“…Post-marketing surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects, namely nausea and allergic skin reactions [50]. A comparison study between moxonidine (0.6 mg/day or 0.4 mg/day) and enalapril (20 mg/day or 10 mg/day) showed similar antihypertensive efficacy in the measurements of office blood pressure as well as ambulatory blood pressure, and generally moxonidine was well tolerated without any drug-related adverse events [52,53].…”

Section: Adverse Eventsmentioning

confidence: 96%

Imidazoline Receptor Agonists in Obesity-Related Hypertension: Therapeutic Targeting of the Sympathetic Nervous System

Lambert¹,

Masuo²

2010

IEMAMC

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Obesity, hypertension and obesity-related hypertension are growing health problems. Indeed, hypertension is an important risk factor for cardiovascular disease development, particularly in patients with obesity, diabetes, and metabolic disease. Obese subjects frequently present with hypertension, diabetes mellitus, metabolic disease, and end-organ damage (i.e. end-stage renal damage). In such patients, an integrated cardiovascular risk management approach should be adopted with aggressive blood pressure control being important in patients at high cardiovascular risk. The use of welltolerated antihypertensive agents with protective benefits beyond blood pressure lowering is advantageous. The identification and management of these cardiovascular risk factors are an important part of the overall management of hypertensive patients. Given that patients with obesity or metabolic syndrome are more predisposed to target organ damage, stringent targets for blood pressure control have been set in clinical guidelines; however clinical trial and real-life evidence suggest that these targets are difficult to achieve.The first line of treatment of obesity and metabolic syndrome is weight loss with a lifestyle modification, such as low caloric diet and exercise; however it is difficult to achieve and maintain weight loss. In severe cases, bariatric surgery may be an option, although whether surgery is associated with long term significantly sustained blood pressure reduction is problematic.Sympathetic nervous system activation and insulin resistance are recognized as being important in the pathogenesis of blood pressure elevation in essential hypertension, obesity and the metabolic syndrome. Angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs), which are known of the favorable effects on insulin resistance have therefore been widely used. Recently, several clinical and epidemiological studies have shown that the centrally acting imidazolin receptor agonists which inhibit sympathetic overflow from the brainstem, are highly efficacious, persistent, and well-tolerated antihypertensive agents. Additionally, imidazoline receptor agonists, such as moxonidine or rilmenidine, have been shown to exert beneficial effects not only on blood pressure, but also lipid (reducing free fatty acids) and carbohydrate metabolism (improving glucose tolerance), and neurohormonal parameters (norepinephrine, leptin). Given these additional benefits imidazolin receptor agonists may be a preferable treatment for obesity-related elevation in blood pressure and exert beneficial effects on metabolic and cardiovascular pathogenesis and end-organ damage.The topic of this chapter is central sympathetic nervous inhibition as a treatment for obesity-related hypertension with a particular focus on the possible use of "imidazoline receptor agonists".

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Placebo-controlled Comparison of the Efficacy and Tolerability of Once-daily Moxonidine and Enalapril in Mild to Moderate Essential Hypertension

Abstract: Moxonidine 0.6 mg o.d. and enalapril 20 mg o.d. have similar antihypertensive efficacy.

Cited by 19 publications

References 20 publications

Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension

Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension

Angiotensin vaccination: What is the prospect of success?

Imidazoline Receptor Agonists in Obesity-Related Hypertension: Therapeutic Targeting of the Sympathetic Nervous System

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