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

Electrical stimulation of the dorsal periaqueductal gray matter (DPAG) eliciting flight behavior in awake rats caused an increase in arterial blood pressure (BP), heart rate (HR) and respiration in rats anesthetized with urethane. The hypertension was markedly reduced by 5 mg/kg of intravenously injected hexamethonium or bretylium, virtually abolished by 5 mg/kg of phentolamine and partially antagonized by 0.1 mg/kg of the alpha 1-adrenoceptor blocker, prazosin. The tachycardia induced by DPAG stimulation was partially antagonized by hexamethonium or bretylium and abolished by propranolol (5 mg/kg, IV) or practolol (5 mg/kg, IV), but not affected by N-butylscopolamine (10 mg/kg, IV). Phentolamine increased basal HR and abolished the tachycardic response caused by either brain stimulation or intravenous noradrenaline. Prazosin moderately decreased the response to noradrenaline, but did not affect basal HR or the tachycardia induced by brain stimulation. The increase in respiratory amplitude occurring during brain stimulation was abolished by phentolamine as well as by prazosin, while the increase in respiratory rate was moderately reduced by phentolamine and propranolol. These results demonstrate that the cardiovascular component of the defense reaction of the rat is almost entirely due to a sharp increase in sympathetic tone. They also suggest that the hyperventilation induced by aversive brain stimulation is modulated by central and peripheral adrenergic mechanisms.
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PMID:Neuroeffector mechanisms of the defense reaction in the rat. 665 64

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.
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PMID:Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin. 668 Oct 38

Prazosin sinks the pathologically increased blood pressure, reduces pre- and afterload in myovascular insufficiency and has an interesting influence on plasma lipid fractions with regard to the coronary risk. Prazosin thus intervenes in the three cardiovascular disease processes, which often exist simultaneously, which are mutually caused. Studies which have taken place in the meantime demonstrate the possibilities of Prazosin as a treatment for Raynaud's disease and gangrene. The relatively long bio-availability of the preparation led constantly to the discovery of additional ranges of application, but did not deliver any new findings which would have made restrictions of the original application necessary. On the contrary, Prazosin proved to be especially favourable and capable of being universally applied in the illnesses which frequently accompany hypertension and cardiac insufficiency.
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PMID:[Hypertensive therapy with prazosin. Concomitant cardiovascular, metabolic and respiratory diseases. Proven facts and potential aspects]. 672 80

Prazosin was compared with hydralazine in 39 patients (mean age 49 years), who were already on beta-blockade for arterial hypertension. They all had a resting DBP greater than 100 mm Hg on propranolol 80 mg b i d. They were randomly allocated to prazosin or hydralazine treatment. Blood pressure was measured after 4, 8 and 12 weeks. We noted a significant fall in blood pressure in both groups, in most cases to normotensive levels. Side-effects and other variables of interest are discussed. Together with beta blockade, i e propranolol, both prazosin and hydralazine give good blood-pressure control and no important differences could be found.
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PMID:Peripheral vasodilatation in the treatment of hypertension. Prazosin compared with hydralazine in patients not responding to beta-receptor blockade. 676 Jun 80

The pharmacokinetics of prazosin were studied in 10 patients (7 male and 3 female, Group I) with permanent hypertension and chronic renal failure (serum creatinine 40,5 +/- 5,9 mg/l) and in 10 normal subjects (10 male, Group II). Each patient received a single oral dose of 2 mg of prazosin; serum levels were studied at regular intervals over a ten hour period by spectrofluorometry Clinostatic blood pressure was measured with a mercury manometer in the patients in Group I. The rate of absorption of prazosin was identical in the two groups (t max: I,3 +/- 0,2 h and I,6 +/- 0,4 h). Maximal serum concentrations were significantly higher in Group I (33,5 +/- 3,7 microgram/1 compared to 22,0 +/- 2.5 microgram/l, p less than 0,02) as was the surface under the serum concentration curve plotted against time (206,I +/- 31.I microgram.h.l-1 compared to 99,9 +/- 12,3 microgram.h.l-1, p less than 0,01). Prazosin induced a significant fall in systolic and diastolic blood pressure (-19% and -23% respectively, p less than 0.001) in Group I, 90 minutes after administration, associated with a moderate rise in heart rate (+16%, p less than 0.01). The variation of blood pressure induced by prazosin correlated closely with its serum concentration (p less than 0.001). These results suggest that the bioavailability of prazosin is significantly higher in chronic renal failure and that a reduction of the daily dose should be envisaged in these patients on long-term therapy.
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PMID:[Clinical pharmacology of prazosin in arterial hypertension with chronic renal insufficiency]. 679 30

Prazosin (Minipress; Pfizer), the first purely alpha-blocking antihypertensive agent, was used to treat 22 pregnant patients with moderately severe hypertension (diastolic blood pressure persistently above 95 mmHg at gestational ages ranging from 18 to 33 weeks). Prazosin was used because it is a postsynaptic alpha-blocking agent producing no direct tachycardia or renin stimulation and because its action in producing visceral vasodilation might improve uteroplacental perfusion. Oxprenolol (Trasicor; Ciba), a beta-blocking agent with intrinsic sympathomimetic activity, was added to the prazosin regimen in 12 cases. In this group pregnancy was prolonged for an average of 32 days and 10 infants survived the neonatal period. Fetal loss, mainly due to abortion, was high in the patients who had significant proteinuria, and it was not possible to prolong the pregnancy in these cases. There were no significant maternal, fetal or neonatal side-effects attributable to this combined alpha- and beta-blocking therapy, which may have both theoretical and practical advantages over other current therapies.
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PMID:Prazosin and oxprenolol therapy in pregnancy hypertension. 687 69

Prazosin, a quinazoline derivative, is a peripheral vasodilator used in the treatment of arterial hypertension and more recently, congestive heart failure (CHF). Prazosin is extensively metabolised by the liver and has high first-pass metabolism and low oral bioavailability. In normal healthy volunteers, the time of peak concentration occurs between 1 and 3 hours after oral administration, with wide interindividual variations. The extent of oral absorption seems to be similar for different pharmaceutical forms and is not influenced by the presence of food in the digestive tract. Oral bioavailability of prazosin ranges from 43.5 to 69.3% (mean 56.9%). Prazosin is highly (92 to 97%) bound to human plasma proteins (albumin and alpha 1-acid glycoprotein) and the extent of binding is independent of the plasma concentration of the drug in the range of 20 to 150 ng/ml. Preliminary studies in humans indicate that pathways for biotransformation of prazosin are similar to those observed in the rat and dog. Only 6% of prazosin is excreted unchanged, mainly in the urine. The two main metabolites (0-demethylated) are almost completely excreted in bile. The time course of disappearance of prazosin from plasma after intravenous injecton indicates that prazosin disposition should be described by a model containing at least 2 kinetically distinct compartments. The mean elimination half-life is about 2.5 hours. After intravenous administration, the steady-state volume of distribution has been calculated to be 42.2 +/- 8.9L and the total body clearance 12.7 +/- 1.3L/h. In hypertensive patients with normal renal function, prazosin kinetics do not differ significantly from normals. However, prazosin disposition is modified in chronic renal failure and in congestive heart failure. In both cases, the plasma free fraction of prazosin is increased and plasma elimination half-life is longer. Prazosin kinetics may be expected to be altered in patients with liver diseases. Pharmacokinetic data do not suggest a mechanism to explain the disappearance of the first-dose effect during continued administration of prazosin. Although more investigation is needed to define prazosin kinetics in congestive heart failure and chronic renal failure, the available information about prolongation of elimination half-life, decreased protein binding and increased peak plasma concentrations suggest that prazosin dosage should be titrated cautiously in such patients.
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PMID:Clinical pharmacokinetics of prazosin. 699 81

Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8 +/- 3.6 down to 101.1 +/- 2.5 mmHg, p less than 0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-beta-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; all p less than 0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4 +/- 2.0 ms/mmHg down to 6.6 +/- 1.9 ms/mmHg (p less than 0.05), without an associated change in cardiac vagal inhibition (291.2 +/- 46.2 versus 300.3 +/- 19.2 ms, p greater than 0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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PMID:Prazosin depression of baroreflex function in hypertensive man. 704 70

Prazosin was administered to 16 patients with essential hypertension in an initial dose of 0.5 mg, after which the blood pressure (BP), pulse, and plasma concentrations of prazosin were measured at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours. The dose of prazosin was then increased over 16 to 20 weeks, and similar sequences of measurements were obtained twice. Eleven patients completed the 20-week course. All patients did not respond in a similar way; two distinct patterns of BP and pulse response emerged, although there was no significant difference in the pharmacokinetic parameters, namely, absorption rate constant (Ka), maximum plasma concentration (Cpmax), time to reach the maximum concentration (Tmax), prazosin plasma half-life (T 1/2), elimination rate constant (kel), prazosin plasma concentration-time curve (AUC), and clearance. Patients in Group 1 had a marked reduction (52/30 mm Hg) of BP after the first dose of prazosin, no pulse increase, and needed a small dose of prazosin to maintain an adequate BP response. Patients in Group 3 had a minimal reduction in BP (14/13 mm Hg) after a first dose, a significant pulse increase, and needed a high dose of prazosin to control their BP. We conclude that this effect might be due to a different drug-receptor interaction, and the BP response and dose could be predicted from the response of the first dose of prazosin.
Hypertension
PMID:Prazosin plasma concentration and blood pressure reduction. 706 Nov 32

1 The report presents the effects on blood lipids and uric acid of six different antihypertensive drugs, used alone and of five different combinations of two antihypertensive drugs. 2 Prazosin significantly lowered serum LDL + VLDL cholesterol and total triglycerides. Atenolol lowered LDL + VLDL cholesterol to a smaller but significant extent. Both pindolol and hydrochlorothiazide (HCTH) were without effect, while oxprenolol significantly increased total triglycerides. Propranolol significantly lowered HDL cholesterol and increased total triglycerides and uric acid. 3 The combination prazosin and pindolol had a favourable effect on the lipid profile, while the combination propranolol and HCTH lowered HDL cholesterol but increased total triglycerides. Propranolol and prazosin lowered HDL cholesterol, while methyldopa and HCTH, and HCTH and amiloride were without effect on blood lipids. 4 It is suggested that the metabolic effects of antihypertensive drugs could be of special importance in long-term treatment of mild hypertension.
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PMID:Antihypertensive drugs and blood lipids: the Oslo study. 710 58


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