Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome

Anichkov, D. A.; Na, Shostak; Schastnaya, Olga V.

doi:10.1185/030079904x20277

Cited by 27 publications

(16 citation statements)

References 38 publications

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“…In human studies, beneficial metabolic effects have been detected in diabetic and insulin-resistant subjects, but in unselected hypertensive subjects (Kaan et al, 1995;Lithell, 1998). Similar results have been obtained with another imidazoline agonist, rilmenidine (Meredith and Reid, 2004;Anichkov et al, 2005).…”

Section: Discussionsupporting

confidence: 72%

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Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine

Sun

Ernsberger

2006

J Pharmacol Exp Ther

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The obese spontaneously hypertensive rat (SHROB) is a model of marked insulin resistance with normoglycemia. We sought to determine whether insulin resistance extends to adipocytes and the impact of an insulin-sensitizing imidazoline, moxonidine (4 mg/kg/days for 21 days). Gonadal adipocytes were isolated from SHROB and lean spontaneously hypertensive rat (SHR) littermates. In lean SHR adipocytes, Akt activation by 100 nM insulin peaked at 3 min at 25-fold, whereas SHROB adipocytes showed only 4-fold activation. In dose-response experiments, the maximal response (E max ) was markedly reduced 18.8 Ϯ 2.3 versus 3.7 Ϯ 0.8. Insulin sensitivity was also attenuated, with higher concentrations required for responses (EC 50 ϭ 3.5 Ϯ 0.5 versus 29 Ϯ 3.8 nM). Glucose uptake as determined with [ 3 H]2-deoxyglucose was also less responsive to insulin in SHROB relative to lean SHR. Moxonidine had little or no effect when applied acutely in vitro, but adipocytes isolated from SHROB treated with moxonidine in vivo showed significantly improved responses to insulin, both in terms of Akt activation and facilitation of glucose uptake. Chronic but not acute moxonidine treatment partially restores insulin sensitivity in SHROB adipocytes, suggesting an indirect action of this agent.Obese spontaneously hypertensive rats (SHROB) are markedly insulin-resistant, showing a greater than 20-fold elevation fasting insulin levels in the presence of normal fasting glucose (Friedman et al., 1997;Velliquette et al., 2005). At the cellular level, defects in insulin action have been noted in skeletal muscle and the liver, as indicated by reduced insulin receptor protein, reduced levels of its substrate protein IRS-1, and impaired insulin-induced tyrosine phosphorylation of both proteins (Friedman et al., 1997). In adipocytes and in skeletal muscle, the stimulation of glucose transport by insulin is impaired. However, insulin signaling in adipocytes in the SHROB model has not yet been characterized.Akt (protein kinase B) is a 57-kDa Ser/Thr kinase that plays a key role in the insulin induced PI3K-Akt pathway (Hanada et al., 2004;Osaki et al., 2004). The binding of insulin to its receptors leads to the phosphorylation of PI3K, which then phosphorylates phosphatidylinositols at the 3-position. Then, Akt is recruited to the inner side of plasma membrane due to the interaction between its pleckstrin homology domain and the phosphatidylinositol-(3,4,5)-trisphosphate produced by PI3K. The Thr308 and Ser473 on Akt are then phosphorylated by 3-phosphoinositide-dependent protein kinase 1/2 and mammalian target of rapamycin (Hresko and Mueckler, 2005). Once activated, Akt regulates many cellular functions related to insulin action (Hanada et al., 2004). As a key element in insulin signaling, Akt could be an efficient indicator for cellular insulin response. Here, we measured the phosphorylation level of Akt in corresponding to insulin stimulation as an indicator of insulin sensitivity in isolated rat adipocytes. We hypothesized that the inherent defe...

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Section: Discussionsupporting

confidence: 72%

“…Similar results have been obtained for another imidazoline agonist, rilmenidine (Penicaud et al, 1998;Velliquette and Ernsberger, 2003b;Anichkov et al, 2005). Moxonidine is a selective agonist at I 1 -imidazoline receptors, while also activating ␣ 2 -adrenergic receptors (Ernsberger et al, 1993).…”

supporting

confidence: 71%

Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine

Sun

Ernsberger

2006

J Pharmacol Exp Ther

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“…Although the data from the clinical studies are limited, ACE-I are known to have favorable effects on patients with MetS [20,21]. Their effects on PMI were not assessed.…”

Section: Discussionmentioning

confidence: 99%

Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial infarction in patients with metabolic syndrome

et al. 2015

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Background: Metabolic syndrome (MetS) has been reported as a risk factor for cardiovascular events. The aim of the present study is to investigate the association between chronic angiotensin-converting enzyme inhibitors (ACE-I) therapy and the rate of periprocedural myocardial infarction (PMI) after elective coronary stenting among patients with MetS. Methods: The inclusion criteria were MetS and plan for elective percutaneous coronary intervention. To assess the effect of ACE-I treatment on the incidence of PMI, measurements of cardiac biomarkers (CK-MB mass and troponin I) were performed at baseline and 24 h after the procedure. Results: A total of 459 patients fulfilling the inclusion criteria were recruited to chronic ACE-I treatment and ACE-I naive groups in a 2/1 ratio. Baseline troponin I and CK-MB levels were similar in both treatment groups, whereas they were significantly lower in ACE-I group 24 h after the procedure. Univariate analysis identified body mass index (BMI), LDL cholesterol, nitrate and ACE-I use as significant factors for the development of PMI. Multivariate regression model revealed that body mass index increased and use of nitrate and ACE-I decreased the probability of PMI independent from confounding factors (OR 1.14, p = 0.002 for BMI; OR 0.26, p = 0.01 for nitrate use, OR 0.51,. Conclusions:This prospective observational cohort trial demonstrated that chronic ACE-I therapy was an independent predictor for reduced PMI among patients with MetS who underwent elective coronary intervention. (Cardiol J 2015; 22, 3: 323-329)

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“…The comparable effect of rilmenidine to lisinopril detected by ABPM was recently confirmed in another study in patients with metabolic syndrome. 45 The latter recent study documented comparable metabolic profile of rilmenidine compared to ACE inhibitor, considered to be the leading class in treatment of patients with metabolic abnormalities. Other representative of selective I 1 -imidazoline agonists moxonidine has been also tested for its possible metabolic activity and some favourable results were obtained.…”

Section: Discussionmentioning

confidence: 92%

How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients

et al. 2006

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The aim of the present study was to evaluate effects of long-term treatment with rilmenidine compared with atenolol on lipid and glucose metabolism and cardiovascular remodelling in hypertension. In total, 37 patients with hypertension were randomised to rilmenidine 1-2 mg/day or atenolol 50-100 mg/day for 26 weeks. Standard oral glucose tolerance test with a parallel measurement of insulin and glucose levels was performed. The 'areas under the curve' (AUC) for insulin and glucose were calculated. Plasma lipids, left ventricular mass index (LVMI), and intima-media thickness (IMT) were measured. Brachial artery diameter during reactive hyperaemia was used to test endotheliumdependent vasodilatation (EDVD). Blood pressure reduction was equally achieved in both treatment arms. The fasting glucose level increased in the atenolol group from 4.870.6 to 5.270.7 mmol/l (Po0.01). The AUC of glucose in rilmenidine group decreased from 860793 to 737766 mmol/min/l (Po0.05), and in the atenolol group it increased from 937786 to 989788 mmol/min/l (Po0.05). Rilmenidine showed a positive effect on lipid levels, whereas in the atenolol group a significant decrease of high-density lipoprotein cholesterol was observed. Left ventricular mass index decreased with rilmenidine by 9.6% and by 6.9% with atenolol (Po0.05). Intima-media thickness significantly decreased in the rilmenidine group. Endothelium-dependent vasodilatation slightly increased on in the rilmenidine group, while on in the atenolol group it remained unchanged. Our data suggest that in hypertensive patients central inhibition of sympathetic drive can produce favourable effects on glucose and lipid metabolism compared with standard b-blockade with a similar antihypertensive efficacy. Rilmenidine also provides beneficial effects on cardiovascular remodelling and altered endothelial function in hypertension.

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Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome

Cited by 27 publications

References 38 publications

Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine

Marked Insulin Resistance in Obese Spontaneously Hypertensive Rat Adipocytes Is Ameliorated by in Vivo but Not in Vitro Treatment with Moxonidine

Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial infarction in patients with metabolic syndrome

How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients

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