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

Fifty-five patients with mild to moderately severe essential hypertension were treated with guanabenz (2, 6-dichlorobenzylidene aminoguanidine acetate) in doses from 4 to 16 mg twice daily in a randomized, placebo-controlled study. The patients treated with placebo in the initial phase of the study were subsequently treated with guanabenz. The mean arterial pressure in the guanabenz group decreased from 130.6 to 107.6; that in the placebo group decreased from 129.6 to 126.6 standing and from 126.6 tp 109.9 and 128.8 to 120.5, respectively, supine. The principle adverse effects included sedation, dry mouth, weakness, and tiredness. Of the guanabenz-treated patients 84% had sustained decrease in supine diastolic blood pressure of 10 mm Hg or more, whereas in the placebo-treated patients only 32% had such a response. There was no significant orthostatic hypotension. Guanabenz thus appears to be an effective antihypertensive drug in patients with mild to moderately severe hypertension.
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PMID:Guanabenz in essential hypertension. 31 38

This open crossover study in eight hypertensive patients defined a possible additive effect of oral guanabenz and captopril and determined a safe and effective dose range. Each group of four patients received placebo followed by ascending doses (on alternate days) of either guanabenz (2, 4, 8 mg) or captopril (6.25, 12.5, 25 mg) as initial monotherapy and were subsequently crossed over to the alternate monotherapy. Guanabenz and captopril were given concomitantly in increasing doses--the highest dose for both groups being 8 mg guanabenz/25 mg captopril. When guanabenz and captopril were given concomitantly, blood pressure decreased, both from the values during placebo administration and from the lead-in values recorded before each dose. Mean supine systolic and diastolic blood pressures after combination therapy decreased significantly (P less than .05) in a dose-related manner at most evaluations. The authors conclude that guanabenz and captopril have an additive effect when administered in combination to patients with hypertension.
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PMID:Dose-ranging study to delineate the additive antihypertensive effect of guanabenz and captopril. 203 2

In recent research a new series of specific drugs, one of which is guanabenz (GBZ, 2,6(dichlorobenzyliden)-aminoguanidine) has been introduced into the clinical treatment of centrally mediated hypertension. Guanabenz (GBZ) is considered to be among the most specific alpha 2-adrenergic agonists, acting similarly to clonidine by decreasing the sympathetic outflow from the brain to the peripheral circulatory system. In the present report we show that GBZ displays a significant affinity for beta-adrenoceptors. In displacement studies of the iodinated beta-antagonist [125I]cyanopindolol (CYP) from turkey erythrocyte membranes, the dissociation constant of GBZ was 3.8 microM. Inhibition of the (-) epinephrine induced adenylate cyclase activity by GBZ is competitive, with an apparent dissociation constant of 30 microM. A similar value was obtained by studies of GBZ's effect on the (-) epinephrine-induced [3H]cAMP accumulation in intact turkey erythrocytes. In view of its unexpected affinity for beta-adrenoceptors, we examined the three-dimensional structure of crystalline GBZ. In these studies substantial differences between clonidine and GBZ were observed, despite their strong structural resemblance. These dissimilarities (angle of rotation phi = 39.7 degrees as compared to 76 degrees in clonidine, and the rotational restriction of clonidine as compared to the greater mobility in rotation of GBZ) could explain the difference of specificity between these two compounds.
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PMID:Beta-adrenergic activity and conformation of the antihypertensive specific alpha 2-agonist drug, guanabenz. 285 65

The responsiveness of central nervous system alpha 2-adrenergic receptors in the neural control of renal function was compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) on normal or high sodium intake (3-4 weeks of 1% NaCl for drinking). The responsiveness of central alpha 2-adrenergic receptors was determined by comparing among groups the dose-response curves for the effects of cumulative intracerebroventricular injections of guanabenz (5, 25, and 125 micrograms) on changes in mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion. Guanabenz altered mean arterial pressure similarly in SHR on normal or high sodium intake and in WKY on normal or high sodium intake. High sodium intake shifted the guanabenz-renal sympathetic nerve activity and guanabenz-urinary sodium excretion dose-response curves to the left in SHR and to the right in WKY. The dose-response curves between SHR and WKY on normal sodium intake were similar. Surgical renal denervation or pretreatment with an alpha 2-adrenergic receptor antagonist (rauwolscine, 30 micrograms i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake. We conclude that the responsiveness of central nervous system alpha 2-adrenergic receptors regarding the neural control of renal function is increased by high sodium intake in conscious SHR, but not in conscious normotensive WKY.
Hypertension 1988 Apr
PMID:Sodium responsiveness of central alpha 2-adrenergic receptors in spontaneously hypertensive rats. 289 35

Sodium retention may partially offset the therapeutic action of some antihypertensive agents. To assess the effects of guanabenz on sodium balance, six men with mild to moderate hypertension were placed on diets with constant sodium intake (120 mEq/day) for approximately 4 weeks. After achieving sodium balance, the subjects received guanabenz (16-24 mg daily) for approximately 2 weeks. Mean supine blood pressure decreased from 144/93 to 133/86 mmHg during guanabenz treatment (p less than 0.001). Guanabenz therapy was associated with a decrease in body weight (mean +/- SE) from 85.4 +/- 7.0 to 84.4 +/- 6.8 kg (p less than 0.01). Sodium balance, glomerular filtration rate, plasma renin activity, mean maximal urine osmolality, fluid intake, urine volume, and serum sodium concentration were unchanged during guanabenz therapy. Three additional balance studies were performed during a period of greater sodium intake (180 mEq/day). Although higher doses of guanabenz were required to achieve blood pressure control, sodium balance still was not affected by the drug. Thus, an effective therapeutic dose of guanabenz administered for 2 weeks had no clinically significant effects on sodium or water homeostasis in patients with mild to moderate hypertension.
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PMID:Effects of guanabenz on sodium and water homeostasis. 345 82

The possible participation of the nucleus reticularis gigantocellularis in the hypotension, decrease in cardiac contractility and bradycardia induced by guanabenz was examined in rats that were anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Guanabenz (10 micrograms/kg, i.v.) elicited an initial, transient hypertension, accompanied by an increase in cardiac contractility, followed by a significant and sustained hypotension, as well as decrease in the force and rate of cardiac contraction. In rats receiving bilateral focal electrolytic lesions of the nucleus reticularis gigantocellularis, the same injection produced only the initial transient responses, without the subsequent depressant effects. Microinjection of guanabenz directly into the ventro-medial portion of the nucleus reticularis gigantocellularis, at an ineffective systemic concentration (500 ng), produced significant and prolonged reduction in arterial pressure, cardiac contractility and heart rhythm. On the other hand, local application of the same concentration (500 ng) of guanabenz into the lateral portion of the same nucleus produced only minor hypotension and bradycardia, with no decrease in cardiac contractility. It is concluded that the nucleus reticularis gigantocellularis is at least one of the central sites through which guanabenz may produce its cardiovascular suppressant effects.
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PMID:Participation of nucleus reticularis gigantocellularis in guanabenz-promoted hypotension, decrease in cardiac contractility and bradycardia in rats. 409 59

There is increasing interest in initial therapy of hypertension with sympatholytic agents and the influence of antihypertensive therapy on cardiac and renal function. We treated 26 men with essential hypertension with either guanabenz alone (n = 14) or propranolol alone (n = 12) and assessed blood pressure and renal perfusion before and after 5-7 weeks of treatment. Cardiac performance was evaluated for the guanabenz-treated patients. Both drugs substantially reduced blood pressure without weight gain. During guanabenz therapy, glomerular filtration rate and renal blood flow were preserved, with a fall in renal vascular resistance (from 12,100 +/- 1,500 to 9,300 +/- 1,190 dyne X s X cm-5, p less than 0.01). Propranolol decreased glomerular filtration rate (from 95 +/- 11 to 70 +/- 6 ml/min, p less than 0.05) without significant change in renal blood flow or renal vascular resistance. In guanabenz-treated patients, there was a decline in left ventricular mass (from 290 +/- 23 to 257 +/- 14 g, p = 0.067). Thus, both agents are effective initial therapy in hypertension. Guanabenz treatment also was associated with reduced renal vascular resistance and left ventricular mass.
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PMID:Comparative effects of antihypertensive therapy with guanabenz and propranolol on renal vascular resistance and left ventricular mass. 608 20

Centrally acting agents and the beta-adrenergic antagonists represent two classes of antihypertensive agents recommended for initial monotherapy. Comparisons of the efficacy and safety of the centrally acting agent, guanabenz, with those of propranolol and pindolol in patients with mild to moderately severe hypertension, are reported. In the guanabenz versus propranolol study, mean supine blood pressure decreased by 19/15 mm Hg for 44 guanabenz-treated patients and by 17/15 mm Hg for 52 propranolol-treated patients who completed 6 months of therapy. In the guanabenz versus pindolol study, the mean decrease in supine blood pressure was 17/14 mm Hg for the 12 patients treated with guanabenz and 21/15 mm Hg for the 13 patients who received pindolol and completed 2 months of therapy. If the patients who discontinued therapy for drug-related reasons are considered, the percentages of patients with clinically satisfactory blood pressure reductions were 59% for the guanabenz group versus 62% for the propranolol group and 79% for guanabenz-treated patients versus 64% for pindolol-treated patients. Although adverse effects, including dry mouth, drowsiness, and weakness, were more common among guanabenz-treated patients, these effects generally were mild and became less frequent with continued therapy. The therapeutic efficacy and safety of guanabenz were similar to those of the two beta-adrenergic blocking drugs, propranolol and pindolol. Guanabenz therapy decreased serum total cholesterol (p less than 0.05), whereas propranolol therapy decreased HDL cholesterol (p less than 0.05). Thus, guanabenz did not produce serum lipid abnormalities that may be associated with increased cardiovascular risk.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of a centrally acting antihypertensive agent and beta-adrenergic blocking agents for the treatment of hypertension. 608 30

Abundant evidence exists for the cumulative adverse effects of hypertension and hypercholesterolemia on the progression of coronary heart disease. The antihypertensive drug guanabenz acetate has been shown to lower serum cholesterol levels, but the mechanism for this effect is unclear. To explore this problem, suspensions of rat liver cells were incubated with guanabenz and labeled lipogenic precursors. Guanabenz produced an inhibition of cholesterol production from [14C]acetate that ranged from 10% at 0.005 mM guanabenz to 90% at 0.20 mM guanabenz. Inhibition of cholesterol production from [14C]mevalonate was half as great as inhibition from [14C]acetate. Thus, guanabenz inhibits hepatic cholesterol production at both pre- and postmevalonic sites in the sterol pathway. Synthesis of triglycerides from [14C]palmitate also was inhibited by guanabenz, whereas oxidation of [14C]palmitate to 14CO2 was stimulated. Therefore, the inhibition of triglyceride formation from fatty acid produced by guanabenz may be due to the stimulation of fatty acid oxidation. The clinical effects of guanabenz on serum lipid levels may relate to its direct actions on hepatic cholesterol and triglyceride biosynthesis.
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PMID:Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate. 608 38

Guanabenz is an orally active central alpha 2-adrenoceptor agonist. Its antihypertensive action is thought to result from a decrease in sympathetic outflow from the brain to the peripheral circulatory system as a result of stimulation of central alpha 2-adrenoceptors. In mild to moderate hypertension it is as effective as methyldopa and clonidine in lowering blood pressure when used as the sole treatment. As with these drugs, guanabenz may be combined with a diuretic to increase its blood pressure-lowering effect. The overall incidence of side effects seen with guanabenz was at least as high as with methyldopa or clonidine, and side effects such as drowsiness or dry mouth have been bothersome enough to lead to discontinuation of guanabenz therapy in some patients. However, particularly troublesome effects such as sodium retention, depression or sexual dysfunction which may occur with methyldopa or clonidine have not been reported with guanabenz.
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PMID:Guanabenz. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension. 635 37


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