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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as metabolic syndrome X. With the notable exception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of metabolic syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moxonidine have mixed effects on components of metabolic syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of metabolic syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moxonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moxonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moxonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.
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PMID:The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X. 1502 95

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 endothelium-dependent vasodilatation (EDVD). Blood pressure reduction was equally achieved in both treatment arms. The fasting glucose level increased in the atenolol group from 4.8+/-0.6 to 5.2+/-0.7 mmol/l (P<0.01). The AUC of glucose in rilmenidine group decreased from 860+/-93 to 737+/-66 mmol/min/l (P<0.05), and in the atenolol group it increased from 937+/-86 to 989+/-88 mmol/min/l (P<0.05). 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 (P<0.05). 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 beta-blockade with a similar antihypertensive efficacy. Rilmenidine also provides beneficial effects on cardiovascular remodelling and altered endothelial function in hypertension.
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PMID:How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients. 1654 10

Activation of the sympathetic nervous system plays a major role in the pathogenesis and prognosis of cardiovascular diseases. Rilmenidine is an I(1)-imidazoline receptor agonist that reduces blood pressure by modulation of central sympathetic activity, but the effects of low-dose rilmenidine on the hemodynamic responses to physiological maneuvers that increase adrenergic drive is not known. To assess the effects of low-dose rilmenidine on the hemodynamic responses to stress, 32 healthy subjects (20-56 years old) underwent acute physical exercise (n = 15, individualized ramp protocol on treadmill) and mental stress (n = 17, word color Stroop and mental arithmetics tests) two hours after the oral administration of 0.5 mg of rilmenidine (RIL) or placebo (PLA) following a randomized, double-blind, placebo controlled crossover study. No subject complained of any side effect. Rilmenidine reduced peak exercise heart rate (PLA: 187 +/- 7; RIL: 181 +/- 9 bpm; P = 0.003), but did not modify peak aerobic power (VO(2max) - PLA: 41.7 +/- 6.2; RIL: 42.3 +/- 6.7 ml/kg/min; P = 0.26). During mental stress, rilmenidine inhibited the peak systolic (PLA: 123 +/- 10; RIL: 114 +/- 8 mmHg; P = 0.02) and diastolic (PLA: 86 +/- 7; RIL: 81 +/- 7 mmHg; P <0.05) blood pressure responses. In conclusion, rilmenidine reduced the hemodynamic response to physical and mental stress stimuli without limiting exercise capacity. These results support the concept that rilmenidine, at a dose lower than the ones recommended to treat hypertension, reduced the myocardial oxygen demand to stress and may carry potential clinical impact.
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PMID:Reduced hemodynamic responses to physical and mental stress under low-dose rilmenidine in healthy subjects. 1676 Nov 92

Rilmenidine is an alpha 2 adrenoreceptor agonist used in the treatment of mild and moderate hypertension. In this study, a fast and accurate liquid chromatographic method with tandem mass spectrometric detection has been validated in order to assure quantification of rilmenidine in human serum. The fragmentation pathway of protonated rilmenidine was studied using high-resolution mass spectrometry (HRMS). This study compared selectivity, linearity, accuracy, precision, extraction efficiency, matrix effect and sensitivity using common liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. The limit of quantitation for both extraction techniques was 0.1 ng/ml. Several differences between the LLE and SPE have been observed in terms of linearity, accuracy, precision and matrix effect. Additionally, the advantages of SPE included less manual work load and increased recovery of rilmenidine in human serum to approximately 80% (LLE, 57%). The developed method involving SPE was found to be accurate (relative error (RE) < 5%), reproducible (relative standard deviation, RSD < 7%), robust and suitable for quantitative analysis of rilmenidine in serum samples obtained from patients under antihypertensive treatment.
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PMID:Development of a fast LC-MS/MS method for quantification of rilmenidine in human serum: elucidation of fragmentation pathways by HRMS. 2081 39


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