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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In essential hypertension, ventricular function is determined primarily by the degree of hypertrophy (myocardial factor) and by the organic complications in the coronary artery (coronary factor). Ventricular function is inversely correlated with ventricular size and systolic wall stress, inasmuch as ventricular function diminishes when these two variables increase. Coronary reserve is reduced even in hypertensive hypertrophy without evidence of coronary artery disease. MVO2 per mass unit is directly correlated with systolic wall stress per cross-sectional area of the left ventricular wall. It is concluded that the appropriateness of left ventricular hypertrophy, as a result of mass-to-volume ratio and stress, is a major determinant of left ventricular performance, of coronary blood flow, and of myocardial oxygen consumption. Pharmacotherapeutical means of reversing cardiac hypertrophy (prazosin, clonidine, enalapril, and nifedipine) were analyzed in concentrically, as well as eccentrically, hypertrophied left ventricles. Regression of cardiac hypertrophy, i.e., therapeutic intervention on a critical precursor of hypertensive congestive heart failure, can be obtained by various antihypertensive agents. Prazosin, calcium channel blockers, and angiotensin converting enzyme inhibitors as well as a combined treatment regimen using alpha-receptor blockers together with diuretics and vasodilators can all induce regression of hypertrophy associated with an improvement in left ventricular function. Moreover, an improved coronary reserve may reduce the ischemic risk of the hypertrophied myocardium. However, not all antihypertensive drugs seem equally effective in bringing about coronary regression of left ventricular hypertrophy (LVH). No regression or little regression has been found with diuretic monotherapy despite a satisfactory reduction in blood pressure. On the other hand, a trend towards a regression has been observed in patients in whom treatment with clonidine significantly reduced catecholamines. Recent experimental data in spontaneously hypertensive rats indicate that the impaired coronary reserve can be significantly improved by the long-term administration of blood pressure lowering agents, e.g., by nifedipine or by the combination of metoprolol plus hydralazine.
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PMID:Regression of myocardial and coronary vascular hypertrophy in hypertensive heart disease. 246 73

Selective alpha 1 adrenergic receptor blocking agents lower blood pressure by reducing the increased peripheral vascular resistance that characterizes essential hypertension. Prazosin and terazosin have been shown to be well tolerated in clinical practice and seldom cause impotence or metabolic abnormalities. The most common adverse effects--dizziness, headache, and asthenia--are generally well tolerated and infrequently lead to discontinuation of therapy. First-dose syncope can usually be avoided by initiating therapy with low doses administered at bedtime. Finally, the alpha 1 receptor antagonists do not adversely affect such cardiovascular risk factors as hypokalemia, serum lipid profile, and left ventricular hypertrophy. In fact, alpha 1 antagonists reduce total cholesterol and low-density-lipoprotein plus very-low-density-lipoprotein cholesterol and thus may contribute to the overall management of cardiovascular risk by blood pressure reduction and improvement of the serum lipid profile. Since the goal of treating chronic essential hypertension is to improve morbidity and mortality, the choice of therapy should be influenced by the agent's ability to modify as many risk factors as possible. Alpha 1 adrenoreceptor antagonists beneficially impact several cardiovascular risk factors and thus merit consideration as first-line antihypertensive therapy.
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PMID:New perspectives on selective alpha 1 blockade. 257 43

The efficacy and safety of prazosin GITS (gastro-intestinal therapeutic system), a new extended-release once-a-day formulation, were assessed both as monotherapy in mild essential hypertension and in combination with a diuretic in moderate essential hypertension in two multicenter, double-blind, placebo-controlled trials. Prazosin GITS (Minipress XL) given once daily in doses of either 10 or 20 mg significantly reduced sitting and standing systolic and diastolic blood pressure compared with placebo in both mild and moderate essential hypertension. There were minimal, clinically insignificant changes in heart rate following prazosin-GITS treatment (2.5, 10, and 20 mg) compared with placebo treatment. Prazosin GITS was well tolerated; the most common adverse experiences reported were headache, dizziness, and fatigue. All adverse experiences in the moderate hypertension group and the majority (91 percent) in the mild hypertension group were mild-to-moderate in severity. The results from these multicenter trials demonstrate the efficacy and safety of this new extended-release once-a-day formulation of prazosin in the treatment of patients with mild and moderate essential hypertension.
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PMID:Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin. 266 73

In essential hypertension ventricular function is determined primarily by the degree of hypertrophy (myocardial factor) and by the organic complications in the coronary artery (coronary factor). Ventricular function is inversely correlated with ventricular size and systolic wall stress, inasmuch as ventricular function diminishes when these two variables increase. Even the young hypertensive heart of normal size with no angiographic abnormalities appears to be prone to ischemia, because the coronary reserve is seriously limited even in the absence of coronary stenosis. Unlike ventricular distensibility, myocardial compliance may be normal even in the presence of pronounced myocardial hypertrophy. As myocardial compliance decreases, systolic wall stress increases and ventricular function is reduced. The hypertensive heart, the most common form of an irregular hypertrophy of the ventricular wall, is found in 14% of such cases. Analysis of the degree of hypertrophy shows that the hypertrophy can be inappropriately high (high mass-to-volume ratio, reduced wall stress), appropriate, or inappropriately low (normal mass-to-volume ratio, increased wall stress). Coronary reserve is reduced even in hypertensive hypertrophy without evidence of coronary artery disease. MVO2 per mass unit was directly correlated with systolic wall stress per cross-sectional area of the left ventricular wall. It is concluded that the appropriateness of left ventricular hypertrophy, as a result of mass-to-volume ratio and stress, is a major determinant of left ventricular performance, of coronary blood flow, and of myocardial oxygen consumption. Pharmacotherapeutical means of reversing cardiac hypertrophy (prazosin, clonidine, enalapril, and nifedipine) were analyzed in concentrically, as well as eccentrically, hypertrophied left ventricles. Regression of cardiac hypertrophy, i.e. therapeutic intervention on a critical precursor of hypertensive congestive heart failure, can be obtained by various antihypertensive agents. Prazosin, calcium channel blockers and angiotensin-converting enzyme inhibitors as well as a combined treatment regimen using alpha-receptor blockers together with diuretics and vasodilators can all induce regression of hypertrophy associated with an improvement in left ventricular function. Moreover, an improved coronary reserve may reduce the ischemic risk of the hypertrophied myocardium. However, not all antihypertensive drugs seem equally effective in bringing about coronary regression of left ventricular hypertrophy. No regression or little regression has been found with diuretic monotherapy despite a satisfactory reduction in blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative analysis of cardiac function, geometry, energetics and coronary reserve in hypertensive heart disease. 296 4

Prazosin has been reported to reduce the hypotensive and/or bradycardic effect of clonidine in various animal models. Investigations in humans have given conflicting conclusions about the effectiveness of the combination of clonidine and prazosin. In patients with essential hypertension prazosin significantly reduced the hypotensive effect of intravenous clonidine, but it failed to affect the clonidine-induced bradycardia. This finding means that the combination of prazosin and clonidine is inappropriate in antihypertensive therapy.
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PMID:Prazosin partly blocks clonidine-induced hypotension in patients with essential hypertension. 303 63

The effects of prazosin and atenolol monotherapy on plasma lipid concentrations were compared in 51 patients with mild to moderate essential hypertension. Prazosin monotherapy (mean dose 5.4 +/- 5.3 mg per day) resulted in a significant decrease in total and low-density lipoprotein cholesterol concentrations; these changes were evident at three months and at six to 12 months. Atenolol monotherapy (mean dose 66 +/- 23 mg per day) resulted in a significant increase in plasma triglyceride concentration that persisted during one year of treatment. The deletion of thiazide from the regimen of prazosin plus thiazide resulted in a small stepwise decrease in plasma triglyceride concentration over 12 months of observation. The addition of polythiazide (0.5 mg two to three times weekly) to the regimen of patients in whom acceptable blood pressure was not attained with prazosin or atenolol monotherapy resulted in a decrease in blood pressure, averaging 18.8 mm Hg for systolic and 10.3 mm Hg for diastolic, and a small, though significant, increase in the concentration of low-density lipoprotein cholesterol. It is suggested that the effects of prazosin on plasma lipid composition may be mediated, at least in part, by blocking an action of either the sympathetic nervous system or circulating catecholamines that normally modulate lipoprotein metabolism and might mediate the lipid alterations induced by thiazide diuretics.
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PMID:Effects of prazosin, atenolol, and thiazide diuretic on plasma lipids in patients with essential hypertension. 351 94

This report reviews a number of significant developments in the fields of noradrenergic transmission and adrenergic receptors which suggest that, in addition to the classical postsynaptic adrenoceptors, there are also presynaptic adrenoceptors that help modulate the release of norepinephrine (NE) from peripheral as well as central noradrenergic nerve endings during nerve stimulation. In particular, stimulation of presynaptic alpha-adrenoceptors reduces this release of transmitter and the reverse is observed after blockade of these receptors. Clearcut pharmacological differences exist between the postsynaptic alpha 1-adrenoceptors that mediate the responses of certain organs and the presynaptic alpha 2-adrenoceptors that modulate the NE release during nerve stimulation. Therefore, subclassification of alpha-adrenoceptors into alpha 1 and alpha 2 subtypes is warranted but must be considered to be independent of the anatomical location of these receptors. Some noradrenergic nerve endings have also been shown to possess beta-adrenergic receptors, the stimulation of which increases the quantity of transmitter released by nerve impulses. Physiologically, these receptors could be activated by circulating epinephrine (E) and be involved in essential hypertension. A third type of catecholamine receptor found at the noradrenergic nerve ending is the inhibitory dopamine (DA) receptor, which might be of significance in the development of new antihypertensive agents. Application of these new concepts of noradrenergic neurotransmission and the subclassification of alpha-adrenoceptors to the treatment of hypertension is presented. Clonidine, for example, appears to be a potent alpha 2-adrenoceptor agonist; the central receptor involved in its antihypertensive action is pharmacologically an alpha 2-type but located postsynaptically. Clonidine also induces activation of peripheral presynaptic alpha 2-adrenoceptors, which might contribute to its cardiovascular action. The antihypertensive effects of alpha-methyldopa are related to the formation of alpha-methylnorepinephrine, a preferential alpha 2-adrenoceptor agonist, which can stimulate peripheral presynaptic alpha 2-adrenoceptors leading to a decrease of NE release and a reduction in sympathetic tone. Prazosin is a new antihypertensive agent the mechanism of action of which involves a selective blockade of postsynaptic alpha 1-adrenoceptors. This drug does not antagonize several effects of clonidine that are mediated via alpha 2-adrenoceptors. The mechanisms presently considered to account for the antihypertensive activity of beta-adrenoceptor blocking agents are numerous. It is proposed that blockade of peripheral presynaptic facilitatory beta-adrenoceptors could be of significance in the antihypertensive action of these drugs.
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PMID:Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. 610 28

We investigated the relevance of the selective alpha 1-adrenergic receptor blockade produced by prazosin to its blood pressure-lowering efficacy in man. The hemodynamic and neuroendocrine responses to the acute and chronic oral administration of prazosin and phenoxybenzamine were compared in a randomized, double-blind, placebo-controlled, crossover study of 11 patients with essential hypertension. These responses were also evaluated during lower body negative pressure and dynamic bicycle exercise, which produce potent but diversified activation of the sympathetic nervous system. In the acute studies, arterial blood pressure decreased to similar levels with prazosin or phenoxybenzamine; however, hemodynamic and neuroendocrine responses differed both before and during sympathetic nervous system activation. Prazosin lowered arterial blood pressure by reducing total peripheral resistance (p less than 0.05). In contrast, phenoxybenzamine produced a modest reduction in cardiac output (8%, p less than 0.05) with little change in total peripheral resistance, forearm vascular resistance or forearm blood flow. Additionally, plasma norepinephrine concentration and heart rate rose to significantly higher levels with prazosin (p less than 0.02) than with phenoxybenzamine, a difference that was most evident with lower body negative pressure or dynamic exercise. Baroreceptor control of arterial pressure homeostasis was preserved with both agents, except during marked degrees of cardiovascular stress. With chronic therapy, the circulatory responses adapted to the alpha-adrenergic antagonists, and both drugs produced similar hemodynamic and neuroendocrine profiles. The differences with acute administration may be the result of a more rapid onset of action and a more marked degree of alpha-adrenergic blockage with prazosin than with phenoxybenzamine therapy, rather than to any difference in their alpha 1- and alpha 2-adrenergic receptor blocking properties. Moreover, the findings of the present study suggest that the prejunctional alpha 2-receptor, autoinhibitory to sympathetic neuronal norepinephrine release, is of no functional significance in patients with essential hypertension.
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PMID:Hemodynamic and neuroendocrine responses to acute and chronic alpha-adrenergic blockade with prazosin and phenoxybenzamine. 612 77

1. Prazosin (2 mg, p.o.) was administered to nine patients with essential hypertension while intra-arterial pressure was recorded by an Oxford portable apparatus. In all patients, 30 min-3 h after the administration, systolic and diastolic pressure fell on assuming the upright posture and four patients fainted. No correlation was found between the degree of fall in pressure and the plasma concentration of the drug. Acute expansion of the plasma volume by means of 6% Dextran infusion reduced the orthostatic blood pressure fall in all cases and a significant inverse correlation was found between plasma volume and orthostatic fall of pressure. 2. After ten days of continuous treatment with prazosin, 2 mg daily, a significant decrease in blood pressure was observed while orthostatic hypotension disappeared, probably due to the plasma volume expansion induced by the drug.
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PMID:Orthostatic hypotension after the first administration of prazosin in hypertensive patients: role of the plasma volume. 616 95

Prazosin, a selective antagonist of postsynaptic alpha-adrenoreceptors, was used to investigate the influence mediated by the juxtaglomerular alpha-adrenoreceptors on renin release in man. We studied, in seven patients with essential hypertension, the acute effects of 0.25 mg prazosin, given intravenously, on blood pressure and plasma renin activity, the degree of alpha-blockade induced by the drug being assessed by comparing the increments in blood pressure following a test dose of phenylephrine before and after prazosin administration. We also measured the increments in plasma renin activity in response to beta-adrenergic stimulus consisting of an isoproterenol challenge, before and during the prazosin induced alpha blockade. Prazosin infusion caused, within 20 min, a marked reduction of the pressor response to phenylephrine, a significant increment in plasma renin activity, and no change in blood pressure. The increments in renin in response to isoproterenol were significantly greater, both in absolute and percent values, after rather than before prazosin. These results indicate that the increase in renin during systemic alpha 1-adrenoreceptor blockade may be independent of the fall in blood pressure and support the view that the juxtaglomerular alpha 1-adrenoreceptors participate in the regulation of renin release with an inhibitory action, which antagonizes the stimulating influence of the beta-adrenoreceptors.
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PMID:Dissociation of the effects of alpha 1-adrenergic blockade on blood pressure and renin release in patients with essential hypertension. 617 32


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