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

The primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The rapid resetting of arterial baroreceptor afferents toward any sustained new level of blood pressure ensures that the reflex acts as an effective buffer of short-term blood pressure fluctuations that accompany daily life but also ensures that arterial baroreflexes play little role in setting the long-term level of blood pressure. Nevertheless, the minimization of blood pressure variability by baroreflex mechanisms is important as studies suggest that a diminished baroreflex is an independent risk factor or sudden death after myocardial infarction. In hypertensive humans and animals, the baroreflex control of heart rate is diminished. Using the steady-state method for assessment of the cardiac baroreflex in rats, we have shown that the change in baroreflex sensitivity is due to a reduction in the vagal range. Although the cardiac sympathetic component of the baroreflex is normal, the level of cardiac sympathetic activity is enhanced, particularly in young hypertensive rats. We have shown that there is a stronger inverse relationship between vagal heart rate range and levels of cardiac hypertrophy than with other variables, such as blood pressure, hypertension, or indexes of vascular hypertrophy. Treatments that reduce cardiac hypertrophy restore cardiac vagal function. Centrally acting antihypertensive agents increase the sensitivity of vagal baroreceptor heart rate reflexes, mainly through an action on central alpha 2-adrenoceptors. They also reduce cardiac sympathetic activity and diminish cardiac sympathetic baroreflexes through a non-alpha 2-adrenoceptor, possibly an imidazoline receptor mechanism. Both of these effects are beneficial in hypertension, where cardiac sympathetic function is enhanced and vagal activity is reduced. Thus, these actions would be expected to cause a desirable reduction in blood pressure variability. The effect of hypertension on baroreflex control of sympathetic vasomotor function is less clear. Studies have shown diminished, normal, and enhanced sympathetic vasomotor baroreflex control. Basal renal sympathetic drive, however, appears to be increased in human essential hypertension. Our studies in conscious rabbits have shown that rilmenidine reduces renal sympathetic baroreflex function. Rilmenidine acts principally at the level of the rostral ventrolateral medullary imidazoline receptors to markedly reduce the basal renal sympathetic nerve activity and the maximum response to transient fluctuations in blood pressure. Thus, in addition to their antihypertensive actions, centrally acting agents, such as rilmenidine, reduce cardiac and renal sympathetic baroreflex responses and increase cardiac vagal baroreflex sensitivity. This provides an ideal profile of action for the restoration of baroreflex function in addition to reversal of cardiac and vascular hypertrophy in hypertension.
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PMID:Baroreflexes and cardiovascular regulation in hypertension. 864 10

This study was aimed to determine the effects of rilmenidine, an hypertensive drug, in an animal model of hypertension associated with insulin resistance, i.e. rats fed on a high fructose diet. Wistar rats were fed during four weeks either on a standard diet (S) or on a high fructose diet (F, 34.5% de fructose). In half of the F groups, rilmenidine (1 mg/kg/day) was added to the drinking water during the two last weeks of the diet (FR). Arterial blood pressure as well as insulin efficiency were determined at the end of the four weeks. Body weight gain was higher in F than in S rats (66 +/- 8 g versus 45 +/- 8 g; p < 0.05), this was prevented by rilmenidine treatment (32 +/- 2 g). Arterial systolic blood pressure was increased in F rats (162 +/- 2 vs 155 +/- 2 mmHg; p < 0.05), rilmenidine brought this value back to normal (149 +/- 3 mmHg). During the euglycemic hyperinsulinemic clamp, glucose utilization was lower (10 +/- 1 vs 14 +/- 1.5 mg/min/kg; p < 0.05) and hepatic glucose production higher (1 +/- 0.01 vs 0 mg/min/kg; p < 0.01) in F than in S rats. These changes in insulin action were totally abolished by rilmenidine. These data demonstrate that rilmenidine can ameliorate the deleterious effects of a high fructose diet, i.e. weight gain, hypertension and resistance to the effects of insulin Rilmenidine could represent a potential therapeutic agent for the treatment of hypertension associated with metabolic disorders such as syndrom X and obesity.
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PMID:[Effects of rilmenidine on rats made insulin resistant and hypertensive by a high fructose diet]. 894 87

Rilmenidine (dose of 1 mg once or twice a day) is the first oxazoline compound with antihypertensive properties. Its effects on lipid parameters [total cholesterol, HDL and LDL fractions, triglycerides, apolipoprotein A1 and B, lipoprotein (a)] were compared under double-blind conditions and in parallel groups to those of captopril (50 to 100 mg per day, in 2 divided doses) over a period of 8 weeks, in 51 hyperlipidaemic hypertensive patients [age: 56.3 +/- 1.5 years, systolic and diastolic blood pressure (SBP/DBP): 165.1 +/- 2.0/99.1 +/- 0.6 mmHg, LDL cholesterol: 5.38 +/- 0.16 mmol/L]. No significant difference was demonstrated between the groups on inclusion for any of the clinical parameters (SBP, DBP, heart rate (HR)) and laboratory parameters, apart from apolipoprotein A1, for which the mean value was higher in the rilmenidine group than in the captopril group (p < 0.05). No difference between the groups was demonstrated during the 8 weeks of treatment for the course of blood pressure: SBP and DBP decreased by 20.5 and 13.9 mmHg, respectively, in the rilmenidine group and by 21.3 and 13.1 mmHg in the captopril group (no significant difference: NS). HR decreased by 0.3 beats per minute (bpm) in the rilmenidine group and by 4.1 bpm in the captopril group (NS). No statistically significant difference in lipid parameters was observed between the two groups. No clinically significant variation in any of the lipid parameters was observed after 8 weeks of treatment with rilmenidine or captopril. These results confirm the antihypertensive efficacy and neutrality of rilmenidine on lipid metabolism over a period of 8 weeks. Rilmenidine therefore represents a useful alternative in the first-line treatment of hypertension in hyperlipidaemic hypertensive patients.
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PMID:[Effects of rilmenidine (hyperium) on lipid balance in hyperlipidemic hypertensive patients. Randomized, controlled, double-blind 8-week study vs. captopril in parallel groups]. 903 99

SYMPATHETIC NERVOUS SYSTEM AND HYPERTENSION: Biochemical, electrophysiological, pharmacological and haemodynamic findings support the existence of sympathetic nervous system activation in primary human hypertension. Analysis of regional sympathetic nervous system function, using both neurophysiological methods for measuring sympathetic nerve firing rates, and neurochemical techniques for quantifying regional noradrenaline spillover to plasma has demonstrated activation of the sympathetic nervous outflows to the heart, the kidneys, and skeletal muscle vasculature, particularly in younger patients. The initiating cause of this sympathetic nervous stimulation is unknown, but estimation of central nervous system noradrenaline turnover in hypertensive patients, using measurements of the washout of noradrenaline and its lipophilic metabolites into the internal jugular veins, indicates that activation of forebrain pressor noradrenergic nuclei is the probable underlying mechanism. CONSEQUENCES OF INCREASED SYMPATHETIC ACTIVITY: The sympathetic activation present in human hypertension no doubt contributes to the blood pressure elevation, and is a legitimate target for therapeutic intervention with imidazoline receptor-binding agents such as rilmenidine. In addition, the sympathetic nervous activation seems to have adverse consequences in hypertensive patients beyond initiating the blood pressure elevation. There is evidence that neural vasoconstriction has metabolic effects, in skeletal muscle impairing glucose delivery to muscle, causing insulin resistance and hyperinsulinaemia, and in liver retarding postprandial clearing of lipids, contributing to hyperlipidaemia. Cardiac sympathetic activation is demonstrably a cause of sudden death in heart failure patients; a comparable arrhythmogenic effect is probable in hypertension. A trophic effect of sympathetic activation on cardiovascular growth is also likely, contributing to the development of left ventricular hypertrophy. Rilmenidine, through its central nervous system actions, has been demonstrated to powerfully reduce sympathetic nervous activity in essential hypertension patients. INHIBITING THE SYMPATHETIC SYSTEM: As the clinical consequences of sympathetic nervous activation in essential hypertension appear to go beyond that of hypertension pathogenesis, extending to a causal influence in atherosclerosis development, cardiovascular hypertrophy and cardiac arrhythmias, it is possible that, of all antihypertensive drugs, those inhibiting the sympathetic nervous system might best reduce cardiovascular risk. This remains to be tested.
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PMID:High blood pressure management: potential benefits of I1 agents. 974 6

Drugs acting within the autonomic nervous system are of particular interest when autonomic abnormalities are implicated in the development and maintenance of various cardiovascular pathologies. For example, it has been documented that in the early stages of hypertensive disease, i.e. hyperkinetic borderline hypertension, a sympathetic hyperactivity associated with a decreased parasympathetic activity results in increased cardiac output and heart rate. Several classes of drugs acting within the central, as well as the peripheral, autonomic nervous system are very efficient in treating hypertensive disease. One class - the second generation of a group of centrally acting drugs selective for imidazoline receptors - has proved beneficial in this respect, because drugs in this class are well tolerated and have interesting additional effects such as their antiarrhythmic action. Rilmenidine and moxonidine are the lead compounds of this class of drugs. Rilmenidine and moxonidine both proved more selective for cerebral imidazoline receptors than the reference drug, clonidine. It was suggested that this selectivity, attributable to their lower affinity for alpha2-adrenoceptors, explains the low incidence of adverse effects (including sedation) associated with these drugs. In addition, potentially beneficial actions on cardiac dysrythmias and congestive heart failure enlarge the therapeutic potential of the second generation of imidazoline-related drugs. This review focuses on the main pharmacological and clinical properties of rilmenidine and moxonidine, paying particular attention not only to their efficacy in hypertension but also to other potential cardiovascular indications.
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PMID:Drugs acting on imidazoline receptors: a review of their pharmacology, their use in blood pressure control and their potential interest in cardioprotection. 1059 61

Rilmenidine is an imidazoline derivative that appears to lower blood pressure (BP) by an interaction with imidazoline (I1) receptors in the brainstem (and kidneys). Rilmenidine is as effective in monotherapy as all other first-line classes of drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists. It is well tolerated and can be taken in combination for greater efficacy. Sedation and dry mouth are not prominent side effects and withdrawal hypertension is not seen when treatment is stopped abruptly. Recently, in addition to a reduction in BP, this agent has been shown to improve glucose tolerance, lipid risk factors, and insulin sensitivity. These changes would be consistent with a reduction in long-term cardiovascular risk, as would recently described actions on the heart (reducing left ventricular hypertrophy) and the kidney (reducing microalbuminuria). Although no data are yet available from prospective long-term outcome studies, rilmenidine could represent an important new development in antihypertensive therapy and the prevention of cardiovascular disease.
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PMID:Update on rilmenidine: clinical benefits. 1172 91

The central antihypertensive drugs such as methyldopa or clonidine have been agents of importance in the therapy of hypertension. Due to the side effects and the rebound hypertensive phenomenon in the case of clonidine, the use of these agents have been clearly diminished. There are several evidences that a new type of receptor, imidazoline receptor, is present in the central nervous system and in the periphery. A specific agonist for these receptors, rilmenidine, has been studied in experimental animals and in hypertensive patients. Clinical studies have shown that rilmenidine exhibits similar efficacy but a better tolerability compared to clonidine. Rilmenidine may represent a good alternative in the therapy of hypertension.
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PMID:Central Acting Antihypertensive Drugs: Past, Present, and Future. 1185 Jun 58

The purpose of this study was to evaluate the chronic effect of rilmenidine on time domain indexes of heart rate variability in patients with mild hypertension. Twenty patients (12 males, eight females; mean age, 47 yr; age range, 38-55 yr), with untreated and newly diagnosed mild hypertension were studied. There was no evidence of diseases other than hypertension. All patients received 1 mg of rilmenidine once daily. If the diastolic blood pressure was still greater than 90 mm Hg after 4 weeks of active treatment, the dose was increased to 2 mg once daily. Twenty-four hour ambulatory electrocardiograms were recorded before, and 4 and 12 weeks after the start of therapy. Time domain parameters of heart rate variability were calculated. Rilmenidine therapy determined a marked decrease in blood pressure. At 4 weeks, rilmenidine induced a significant reduction in systolic and diastolic blood pressure and a further reduction was observed after 12 weeks. At 4 and 12 weeks, time domain parameters of heart rate variability and heart rate were not significantly different in the data obtained before therapy. In conclusion, this study demonstrated that the administration of rilmenidine to patients with mild essential hypertension induced significant reductions in blood pressure, without any significant changes in time domain parameters of heart rate variability.
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PMID:The chronic effect of rilmenidine on heart rate variability in patients with mild hypertension. 1195 11

The short-term (three months) effects of rilmenidine on systemic hypertension induced left ventricular hypertrophy (LVH) and left ventricular systolic and diastolic functions in comparison with those of perindopril and nifedipine-slow release (SR) formulation were studied. The short-term effects of rilmenidine on biochemical parameters and lipid profiles were evaluated. Sixty patients (39 men, 21 women) with a mean age of 59 +/- 14 years and with mild to moderate systemic arterial hypertension were enrolled in three groups. The first group received 1 mg/day of rilmenidine, the second group 4 mg/day of perindopril, and the third group 20 mg/day of nifedipine SR. All drugs induced a similar decrease in systolic and diastolic blood pressure (BP) values. Left ventricular mass (LVM) and LVM index decreased equally in all groups associated with a significant increase in the E/A ratio. The ratio between the reduction in LVM and decrease in mean arterial pressure (LVM/mmHg) was higher in groups 1 and 2. Negative correlations between LVM and LVMI. E/A, and the dv/dt ratio were obtained. Rilmenidine did not change the blood chemistry and lipid profile values. Despite its neutral effect on lipid profile and biochemical parameters. rilmenidine is as effective as perindopril and nifedipine in controlling hypertension and decreasing left ventricular hypertrophy.
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PMID:Short-term effects of rilmenidine on left ventricular hypertrophy and systolic and diastolic function in patients with essential hypertension: comparison with an angiotensin converting enzyme inhibitor and a calcium antagonist. 1458 51

We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced "nonvascular" neuroeffector mechanism. As such, sympathoinhibitory agents such as rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension.
Hypertension 2004 Mar
PMID:Sympathetic responses to stress and rilmenidine in 2K1C rabbits: evidence of enhanced nonvascular effector mechanism. 1474 28


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