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

The hemodynamic effects of rilmenidine (S 3341) were evaluated noninvasively by aortic Doppler velocimetry, M-mode echocardiography and phonocardiography in hypertensive patients treated for 28 days. After a 2-week placebo run-in period, patients with mild hypertension (group I, n = 8, mean diastolic blood pressure [BP] = 97.18 +/- 0.65 mm Hg) received 1 mg of rilmenidine each morning and patients with moderate hypertension (group II, n = 6, mean diastolic BP = 107.62 +/- 1.18 mm Hg) received 1 mg twice daily. The hemodynamic variations in both groups after the first administration (day 1) showed that during the first 3 hours, mean arterial pressure and cardiac index (CI) were significantly reduced, whereas total peripheral resistance (TPR) was increased. From the third to the fifth hour, the decrease in mean arterial pressure was maintained, CI was higher than initial values and TPR decreased, indicating a persistent vasodilator effect. On day 28, hemodynamic variations were similar but of a lower amplitude. Before administration on day 28, a significant decrease in systolic and diastolic BP was observed, demonstrating that the antihypertensive activity of 1 mg was maintained for 24 hours, with a significant reduction in TPR and no modification of CI or stroke index. The M-mode and phonocardiographic left ventricular function indexes remained unchanged. Rilmenidine has a prolonged antihypertensive activity with a chronic vasodilator effect and no negative inotropic effect.
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PMID:Noninvasive study of cardiac structure and function after rilmenidine for essential hypertension. 289 63

A double-blind multicenter trial compared rilmenidine with placebo in the treatment of 126 patients with mild to moderate hypertension after a 4-week placebo run-in period. Patients with mild hypertension (study 1) with mean supine diastolic blood pressure (BP) between 95 and 104 mm Hg received either rilmenidine 1 mg/day (n = 31) or placebo (n = 35) for 4 weeks. In study 2, patients with moderate hypertension (mean supine diastolic BP between 105 and 115 mm Hg) received either rilmenidine 1 mg twice a day (n = 30) or placebo twice a day (n = 30) for 4 weeks. All 61 patients taking rilmenidine completed the study; 8 of the 65 patients taking placebo were withdrawn because of an increase in BP. Rilmenidine significantly reduced mean systolic and diastolic BP compared with placebo in both studies. BP was normalized (systolic less than 160 mm Hg and diastolic less than or equal to 90 mm Hg in 61% of the patients taking rilmenidine as opposed to 23% of those taking placebo (p less than 0.001). There was no significant difference in the incidence of either dry mouth or daytime drowsiness between rilmenidine, 1 mg/day, and placebo. Dry mouth was significantly more frequent with rilmenidine, 2 mg/day, than with placebo, but this difference was transient and no longer significant at the end of the study. No unexpected adverse effects occurred. Rilmenidine as single therapy appears to be effective and well accepted in the management of mild to moderate hypertension, in particular at the 1-mg/day dose, which normalized 84% of mild hypertensive patients and did not induce any significant adverse effects compared with placebo.
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PMID:Efficacy and acceptability of rilmenidine for mild to moderate systemic hypertension. 289 64

The effects of a new alpha 2 agonist (S 3341 or rilmenidine) on blood pressure (BP), glycemic control, lipid metabolism and renal function were investigated during a 16-week open study in 29 insulin-treated diabetic patients with mild to moderate hypertension. There were 17 men and 12 women aged 50.9 +/- 2.2 years (mean +/- standard error of the mean). Duration of diabetes and insulin therapy was 218 +/- 24 and 143 +/- 30 months. After 2 weeks of placebo, systolic and diastolic BP was 165 +/- 3 and 97 +/- 0.5 mm Hg, respectively (supine). Rilmenidine (S 3341) given alone at daily doses of 1 or 2 mg according to the clinical response led to a prompt and sustained decrease of systolic and diastolic BP (159 +/- 4 and 88 +/- 1 mm Hg after 2 weeks; 149 +/- 3 and 85 +/- 1 mm Hg after 12 weeks; p less than 0.01). Seventeen patients (59%) had normal BP (systolic BP less than 160; diastolic BP less than 90 mm Hg, supine) after 12 weeks of S 3341. Diuretics were associated with S 3341 for the nonresponders at week 12; this led to normalization of BP in 90% of the patients at the end of the study. Glycemic control was assessed by home glucose monitoring (5 determinations/1 day per week), 24-hour glucosuria and postprandial plasma glucose at the outpatient clinic (n = 7) as well as by the measurement of the glycosylated hemoglobin. None of these parameters was significantly affected by S 3341.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of systemic hypertension in insulin-treated diabetes mellitus with rilmenidine. 289 67

The relative contributions of imidazoline-preferring receptors (IPR) and alpha 2-adrenoceptors to hypotensive and bradycardic effects of intracisternal (i.c.) rilmenidine were investigated in conscious rabbits. We compared the antagonist potencies of two alpha 2-adrenoceptor antagonists, 2-methoxy-idazoxan (0.001-10 micrograms/kg i.c.), which has very low affinity for IPR, and idazoxan (0.003-30 micrograms/kg i.c.), which has high affinity for blocking IPR. We also compared the i.c. effects of the antagonists on responses to alpha-methyldopa (alpha-MD), a drug with centrally acting alpha 2-adrenoceptor agonist metabolites that have no affinity for IPR. Rilmenidine (22 micrograms/kg i.c.) and alpha-MD (400 micrograms/kg i.c.) produced similar decreases in mean arterial pressure (MAP) (delta MAP = -23 +/- 2 and -24 +/- 2%, respectively) and in heart rate (HR) (delta HR = -11 +/- 1 and -9 +/- 2%, respectively, n = 30). The hypotension and bradycardia produced by alpha-MD and rilmenidine were completely reversed by 2-methoxy-idazoxan, but 2-methoxy-idazoxan was 16 and 9 times more potent at restoring MAP and HR, respectively, after alpha-MD than after rilmenidine. In contrast, idazoxan was more potent in reversing the hypotension elicited by i.c. injections of rilmenidine than that elicited by alpha-MD. Idazoxan, however, had no effect on rilmenidine-induced bradycardia, but did dose-dependently reverse the decrease in HR produced by alpha-MD. In separate experiments, we observed that the doses of each antagonist drug in themselves did not modify MAP nor HR significantly, but a 10-fold higher dose of idazoxan (300 micrograms/kg) caused immediate although brief hypertension and tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rilmenidine-induced hypotension in conscious rabbits involves imidazoline-preferring receptors. 751 34

The aim of the present study is to characterize the cardiovascular effects of rilmenidine and moxonidine, two recently developed centrally acting antihypertensive drugs. Rilmenidine and moxonidine are alpha 2-adrenoceptor agonists and, in addition, possess affinity for imidazoline (I1)-receptors. To determine if alpha 2- or I1-receptors are involved in sympathoinhibition, rilmenidine and moxonidine were compared with UK 14304, an alpha 2-agonist devoid of affinity for I1-receptors, and antagonism by the "pure" alpha 2-adrenoceptor antagonists yohimbine, SK&F86466, and RX821002 was studied. When injected intravenously into conscious rabbits, rilmenidine and moxonidine, on the one hand, and UK 14304, on the other, elicited a similar pattern of effects. Thus, transient hypertension was followed by long-lasting hypotension accompanied by a decrease in heart rate, renal sympathetic nerve firing rate, and plasma norepinephrine concentration. The effects of rilmenidine, moxonidine, and UK 14304 were antagonized by intravenously administered yohimbine, SK&F86466, and RX821002. The effects of moxonidine and UK 14304 were also prevented by yohimbine injected into the cisterna magna. Altogether, the degree of antagonism of the effects of rilmenidine and moxonidine did not differ from the degree of antagonism of the effects of UK 14304. Rilmenidine, moxonidine, and UK 14304 were also given to pithed rabbits in which a constant sympathetic tone was maintained by electrical stimulation of the sympathetic nerves. At doses that caused sympathoinhibition in conscious rabbits, they lowered the plasma norepinephrine concentration markedly. Our experiments show by direct measurement of sympathetic nerve activity and plasma norepepinephrine concentration that rilmenidine, moxonidine, and UK 14304 cause sympathoinhibition. As a consequence, blood pressure and heart rate decrease. The simplest interpretation of the blockade of central sympathoinhibition by the selective alpha 2-adrenoceptor antagonists is that rilmenidine, moxonidine, and UK 14304 primarily activated alpha 2-adrenoceptors. The decrease in plasma norepinephrine in pithed rabbits indicates peripheral presynaptic alpha 2-adrenoceptor-mediated inhibition of norepinephrine release per action potential from postganglionic sympathetic axons and suggests a contribution of this mechanism to the overall reduction in sympathetic tone.
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PMID:Mechanism of sympathoinhibition by imidazolines. 767 73

Centrally acting antihypertensive drugs are recognized to be safe and effective treatment for high blood pressure. Centrally mediated side effects, such as sedation, are commonly dose- and treatment-limiting events. Imidazoline-preferring receptors, while functionally similar to alpha 2 adrenoceptors, are distinguishable not only on the basis of in vitro radioligand binding but also in vivo in terms of side effects. Drugs with an imidazoline structure lower blood pressure but are less likely to impair psychomotor function. A placebo-controlled study compared moxonidine 0.1 mg with clonidine 0.1 mg orally in nine normal subjects. Both active drugs lowered blood pressure compared to placebo (clonidine more than moxonidine). However, psychomotor function and self-scored sedation and dry mouth were significantly affected only by clonidine. In a long-term (4 weeks) double-blind cross-over study in essential hypertension, rilmenidine was well tolerated and had similar effects to those of atenolol on erect and supine blood pressure. Rilmenidine had no effect on a wide range of autonomic and psychomotor tests or on responses to mental or physical stress. Atenolol, by contrast, had the predicted effects of a beta adrenoceptor antagonist on heart rate during exercise and the Valsalva maneuver. Imidazoline-preferring drugs offer a new and realistic approach to antihypertensive therapy with blood pressure reduction not limited by marked sedation within the therapeutic dose range.
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PMID:Clinical pharmacology of drugs acting on imidazoline and adrenergic receptors. Studies with clonidine, moxonidine, rilmenidine, and atenolol. 767 87

The involvement of alpha-2 adrenoceptors or imidazoline-1 receptors in the sympathoinhibitory effect of rilmenidine was investigated in conscious rabbits. Dose-response curves were determined for the effects of rilmenidine as well as of the alpha-2 selective agonist UK 14304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline] on blood pressure, heart rate, renal postganglionic sympathetic nerve activity and the plasma norepinephrine concentration. The interaction with the alpha-2 selective antagonist SK&F 86466 [6-chloro-N-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine] also was studied. Rilmenidine (30-1000 micrograms kg-1 i.v.) and UK 14304 (1-30 micrograms kg-1 i.v.) elicited the same pattern of changes: transient hypertension followed by prolonged hypotension, bradycardia, a depression of sympathetic nerve firing and a fall in the plasma norepinephrine concentration. The ED50 values for these effects increased in the same order for both drugs: plasma norepinephrine fall < hypotension < depression of sympathetic nerve firing << bradycardia. Pretreatment with SK&F 86466 (3 mg kg-1 i.v. followed by an infusion of 1 mg kg-1 hr-1) altered the dose-response curves of rilmenidine and UK 14304 in a qualitatively and quantitatively almost identical manner; a rightward shift of the hypotensive, sympathoinhibitory and plasma norepinephrine level dose-response curves but no change of the dose-response curve for heart rate. The similarity of the effects of rilmenidine and UK 14304, and the almost identical antagonism of SK&F 86466 against either drug, argue against different sites of action of rilmenidine and UK 14304.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the sympathoinhibitory effect of rilmenidine mediated by alpha-2 adrenoceptors or imidazoline receptors? 791 15

The involvement of nonadrenergic imidazoline specific receptors in the central control of the vasomotor tone and in the mechanism of action of drugs bearing an imidazoline structure, or analogs, is now well documented. Imidazoline-specific binding sites were found in many tissues and species. Moreover, until now, it is only in the brainstem that such binding sites are associated with a function: the hypotensive effect of imidazoline-like drugs. Rilmenidine, which is an oxazoline structurally related to the reference imidazolines, exerts a central hypotensive effect of central origin involving imidazoline receptors. The selectivity of rilmenidine for the imidazoline receptors compared to alpha 2-adrenergic receptors could explain the low incidence of sedative side effects observed with this antihypertensive drug. A specific anti-imidazoline radioimmunoassay allowed us to detect the presence of an immunoreactive imidazoline-like substance in human sera. High levels of this immunoreactive substance are associated with high blood pressure in 20-30% of the hypertensive patients. This observation indicates that high levels of this immunoreactive substance in the serum can be associated with some kinds of primary hypertension. The cause-and-effect relation between these 2 phenomena has not yet been determined. This substance is in process of purification; it could be a candidate to be an endogenous ligand of the imidazoline receptors.
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PMID:Role of imidazoline receptors in cardiovascular regulation. 799 82

1. I1 non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2. We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidine, in 1K-1C hypertensive and 1K-sham normotensive rats. Rilmenidine (0, 3, 10, 30 nmol kg-1 min-1) or moxonidine (0, 1, 3, 10 nmol kg-1 min-1) was infused directly into the renal artery (30 gauge needle) of 1K-sham normotensive and 1K-1C hypertensive rats. 3. In 1K-sham normotensive rats, rilmenidine and moxonidine produced dose related increases in urine flow rate, sodium excretion and osmolar clearance. Both rilmenidine and moxonidine failed to increase urine flow rate, sodium excretion and osmolar clearance in 1K-1C hypertensive rats to the same extent as in 1K-sham animals. At comparable doses, rilmenidine had no effect, while moxonidine (3 and 10 nmol kg-1 min-1) did result in a small increase in urine volume and osmolar clearance which was less than that observed in the 1K sham control animals. 4. These studies indicate that the renal effects of non-adrenoceptor, imidazoline receptor stimulation are diminished in 1K-1C hypertensive rats compared with 1K-sham normotensive rats. Whether this decrease in activity of the natriuretic non-adrenoceptor, imidazoline receptors contributes to the increase in blood pressure in the 1K-1C acquired model of hypertension remains to be determined.
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PMID:Attenuated renal response to moxonidine and rilmenidine in one kidney-one clip hypertensive rats. 803 42

Rilmenidine is a novel oxazoline derivative that is effective in the treatment of hypertension. Studies in animals have indicated that rilmenidine may reduce blood pressure without the associated central alpha 2 side effects of clonidine. The aim of this double-blind, crossover, placebo-controlled study was to evaluate the hypotensive and central sedative effects of single oral doses of rilmenidine (1 or 2 mg), clonidine (150 or 300 micrograms), and lorazepam (2.5 mg) in 12 healthy male volunteers. Drug effects were assessed with a test battery composed of resting electroencephalogram, auditory evoked responses (AERs), saccadic eye movements, psychomotor performance, and subjective ratings as well as blood pressure and heart rate. Rilmenidine and clonidine produced similar dose-dependent reductions in blood pressure without an effect on heart rate. Saccadic eye movements were not significantly impaired after rilmenidine (1 mg) treatment in contrast to after clonidine (150 micrograms) treatment. Peak saccadic velocity was impaired by all drugs except rilmenidine (1 mg), which was indistinguishable from placebo. The electroencephalographic spectral analysis also demonstrated greater sedation with lorazepam than with the other drugs and greater vigilance with placebo and rilmenidine (1 mg) than with lorazepam. AERs showed a differentiation in sedative effects between lorazepam and clonidine (300 micrograms) relative to placebo, rilmenidine (1 mg), and clonidine (150 micrograms). These results are consistent with the hypothesis that at lower doses, rilmenidine may act preferentially through imidazoline receptors, whereas at higher doses, alpha 2-adrenoceptors may become activated.
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PMID:Effects of rilmenidine and clonidine on the electroencephalogram, saccadic eye movements, and psychomotor function. 864 6


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