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

Hypertension in various experimental models, including spontaneously hypertensive rats (SHR), is associated with elevated rates of vascular collagen synthesis. The sympathetic nervous system is an important factor in the etiology of hypertension in SHR. The primary purpose of this study was to determine the effects of the alpha 1-adrenergic receptor antagonist doxazosin on aortic collagen synthesis and on systolic arterial pressure in SHR. Doxazosin was administered either short-term (20 or 200 mg/kg/day by gavage over 5 days) or long-term (0.02 or 0.20 g/L in the drinking water over 8 weeks). Rates of collagen synthesis were determined by incubating aortic segments with 14C-proline in vitro and then measuring either the formation of 14C-hydroxyproline by means of high-performance liquid chromatography, or the amount of radioactivity liberated by collagenase digestion. Systolic arterial pressure was monitored with the standard tail-cuff technique. Both doses of doxazosin depressed aortic collagen synthesis at 8 weeks of treatment, but neither dose had any effect at 4 weeks. In the short-term study only the higher acute dose of doxazosin significantly reduced aortic collagen synthesis; the lower dose had no effect. In the short-term study doxazosin reduced systolic arterial pressure, with a maximum effect at 1-2 days. Tolerance to the depressor effect developed over the remaining 3-4 days, especially with the higher dose. In the 8-week study, the lower doxazosin dose had no effect on systolic arterial pressure, and the higher dose exerted a biphasic effect, moderately but significantly reducing systolic arterial pressure at 1 and 8 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of doxazosin on vascular collagen synthesis, arterial pressure and serum lipids in the spontaneously hypertensive rat. 244 37

The effects of once-daily therapy with doxazosin (1 to 8 mg/day) on exercise capacity, left ventricular performance and hemodynamics (radionuclide ventriculography) were compared with those of atenolol (50 to 100 mg/day) and placebo in a randomized, double-blind crossover trial in 16 patients (9 men) with mild hypertension. Both medications controlled blood pressure (BP) to a similar degree (mean BP was 150 +/- 12, 137 +/- 17 and 141 +/- 14 mm Hg for placebo, atenolol and doxazosin, respectively) but by different mechanisms. Changes during maximal semierect bicycle exercise were similar to those seen at rest. Doxazosin decreased total peripheral resistance and maintained cardiac output, whereas atenolol decreased cardiac output. Exercise capacity (136 +/- 56 watts with placebo) was maintained by doxazosin (135 +/- 56 watts) but decreased with atenolol (122 +/- 55 watts). Compared with atenolol, doxazosin slightly increased the left ventricular ejection fraction at rest and during exercise. The significance of this study is in the choice of a first-line antihypertensive agent. Both are once-a-day medications that control BP. However, doxazosin does so by improving the abnormal physiology of essential hypertension and, consequently, does not adversely affect exercise performance.
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PMID:Comparison of doxazosin and atenolol in mild hypertension, and effects on exercise capacity, hemodynamics and left ventricular function. 252 29

We have studied the contribution of neurohumoral and structural factors to pressor responsiveness and peripheral resistance in mild/moderate hypertension. Pressor responses to intravenous infusions of phenylephrine (an alpha1 agonist) and angiotensin II were studied in groups of patients with essential hypertension before and after treatment, for 6 weeks with either nifedipine (20 mg bid), enalapril (20 mg daily) or doxazosin (2 mg daily). All drugs lowered blood pressure to a similar extent. Pressor responsiveness to both phenylephrine and angiotensin II showed wide intersubject variation when expressed as the dose of agonist required to raise mean arterial pressure by 20 mmHg (PD20). A group of age-matched normotensive controls showed a similar PD20 for phenylephrine to hypertensives. Angiotensin 11 sensitivity was greater in hypertensives. Drug treatment had different effects in hypertensive patients. Doxazosin, an alpha blocker, reduced the responsiveness to phenylephrine but had no effect on responses to angiotensin II. Nifedipine attenuated responses to both agonists while treatment with enalapril increased responsiveness to both phenylephrine and angiotensin II. We have not found evidence of systematic differences in alpha 1 receptor responses in hypertensives and different "vasodilator" drugs can lower blood pressure with widely different effects on adrenergic and non-adrenergic vascular responses.
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PMID:Pressor responsiveness in essential hypertension and the effects of treatment with an alpha blocker, calcium antagonist or ACE inhibitor. 256

Doxazosin is the latest in a series of highly selective postsynaptic alpha 1-adrenoceptor inhibitors. It is readily absorbed, with high bioavailability and a relatively long plasma half-life, neither of which property is influenced by age. This accounts for the prolonged pharmacologic activity of doxazosin following a single oral dose. Its prime pharmacodynamic activity resides in its ability to counter sympathetic vasoconstriction of the systemic arteriolar resistance vessels and venous capacitance system, which enables the drug to target the major pathophysiologic abnormality in hypertension, i.e., the generalized systemic arteriolar constriction. The widespread vasodilation induced by doxazosin relieves both cardiac preload and afterload and, consequently, reduces left ventricular wall stress and myocardial oxygen consumption. In hypertension, doxazosin reduces blood pressure both at rest and during exercise by reduction of systemic vascular resistance without precipitating substantial reflex cardiac stimulation. The effects are maximal on the standing blood pressure between two and four hours after ingestion; due to doxazosin's relatively slow absorption, postural hypotension is infrequent. Its antihypertensive activity is maintained over 24 hours following a single oral dose, and the optimal dose range is 2 to 8 mg once daily. The antihypertensive efficacy of doxazosin has been shown to be comparable with that of other alpha-adrenoceptor inhibitors, beta-blocking drugs, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors. In contrast to other conventional antihypertensive drugs, a unique feature of alpha-adrenoceptor-inhibiting drugs, including doxazosin, is their ability to reduce the plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and to increase high-density lipoprotein cholesterol concentration. This contrasts with the opposite effect on lipid levels induced by hydrochlorothiazide and atenolol seen in comparative studies. Side effects show no predilection for any organ system, and the overall incidence of such effects compares well with those of other commonly used antihypertensive drugs. This unique combination of antihypertensive efficacy and favorable effect on blood lipid levels indicates that once-daily treatment with doxazosin holds considerable promise in the treatment of hypertension, both from the point of view of its antihypertensive efficacy and also from its primary preventative potential.
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PMID:Clinical pharmacotherapeutics of doxazosin. 256 22

Control of high blood pressure has failed to reduce the risk of atherosclerotic coronary heart disease (CHD). Hypercholesterolemia, which is common among hypertensive patients, cigarette smoking, and hypertension are the major risk factors for CHD. To minimize CHD risk, elevated blood pressure and atherogenic lipid levels should be lowered, but various antihypertensive agents appear to adversely affect lipid levels, actually precluding the CHD risk reduction expected from blood pressure control. Doxazosin, a once-daily, long-acting, alpha 1-adrenergic inhibitor, not only is effective therapy for essential hypertension but also has a favorable impact on lipids. During controlled studies of doxazosin's antihypertensive efficacy, the following blood lipid levels were measured: total cholesterol, total triglycerides, high-density lipoprotein (HDL) cholesterol (including HDL2 and HDL3), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein cholesterol, and apoproteins (apos) AI and B. Results showed total cholesterol (-0.8 to -8.9 percent), total triglycerides (-5.0 to -17.4 percent), and LDL (-9.0 to -16.9 percent) were reduced. The positive prognostic indicators, HDL (+0.7 to +13.0 percent) and HDL:total cholesterol ratio (+3.1 to +26.3 percent), were increased. Apo B decreased, but apo AI remained unchanged. In these hypertension studies, doxazosin has favorably reduced two major CHD risk factors. As part of a new, long-term, controlled, multicenter trial, the prospective benefits of these risk factor reductions on CHD morbidity and mortality will be quantified for doxazosin and other antihypertensive agents.
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PMID:Review of the effects of doxazosin, a new selective alpha 1-adrenergic inhibitor, on lipoproteins in patients with essential hypertension. 256 25

The antihypertensive efficacy of the new alpha 1-adrenoceptor antagonist doxazosin is described, and its selectivity for alpha 1-adrenoceptors is reported from both in vivo and in vitro studies. Groups of beagle dogs with chronic perinephritic hypertension were given doxazosin orally, and systolic blood pressure was recorded indirectly from an exteriorized carotid loop. Dogs given doxazosin 0.5 mg kg-1 daily for 10 days showed consistent daily falls in systolic pressure in addition to a progressive reduction in daily pre-dose pressures. A clear indication of antihypertensive action in excess of 24 h post dose was evident. Heart rate changes were minimal. In pentobarbitone anaesthetized dogs pretreated with desimipramine, doxazosin 10-500 micrograms kg-1 i.v. reduced responses of the nictitating membrane to electrical stimulation of the vagosympathetic-depressor nerve trunk (an alpha 1-adrenoceptor response) but had no effect on the chronotropic response of the heart to electrical stimulation of the ansa subclavia. In contrast, the prejunctional alpha 2-adrenoceptor antagonist activity of yohimbine 10-100 micrograms kg-1 i.v. was manifest as a marked dose-related increase in both the heart rate and nictitating membrane responses. The lack of effect of doxazosin on postjunctional alpha 2-adrenoceptors in vivo was demonstrated in the anaesthetized cat. Doxazosin at 50 and 100 micrograms kg-1 i.v. inhibited pressor responses to injected phenylephrine (an alpha 1-adrenoceptor agonist) but had no effect on pressor responses to either alpha-methylnoradrenaline (an alpha 2-adrenoceptor agonist) or angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The alpha 1-adrenoceptor antagonist profile of doxazosin: preclinical pharmacology. 287 57

Hypertension and hypercholesterolemia are 2 major risk factors for atherosclerotic coronary artery disease (CAD). Elevations of both blood pressure and serum cholesterol levels should be reduced to control CAD risk. Doxazosin is a once-daily, long-acting, selective alpha 1-adrenergic inhibitor that is effective for the treatment of essential hypertension. During controlled studies of doxazosin's antihypertensive efficacy, 3 serum lipid parameters were measured; total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol. In 10- to 12-week placebo-controlled studies, 142 doxazosin-treated patients were compared with 155 placebo-controlled subjects. Doxazosin patients had an increase of 8.9% in the HDL/total cholesterol ratio (p less than 0.05), whereas total cholesterol, HDL cholesterol and triglyceride levels were not significantly different between the 2 study groups. During a 52-week comparison of doxazosin versus atenolol, doxazosin treatment was associated with a significant decrease in total triglyceride levels (5%; p less than 0.001) and increases in HDL cholesterol levels (3.9%; p less than 0.01) and HDL/total cholesterol ratio (5.4%; p less than 0.0001). Doxazosin is an effective antihypertensive agent that has a favorable impact on serum lipid levels, thereby promoting a beneficial effect on 2 major CAD risk factors.
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PMID:Plasma lipid lowering effects of doxazosin, a new selective alpha1 adrenergic inhibitor for systemic hypertension. 288 53

Doxazosin is a competitive inhibitor of norepinephrine at alpha 1 adrenoceptors on vascular smooth muscle, where it blocks vasoconstriction. Twenty-four patients with mild hypertension were treated with either doxazosin or placebo for 6 weeks. Supine and upright mean arterial pressures decreased by 9 and 12 mm Hg, respectively, in patients receiving doxazosin. This decrease was significantly more than the blood pressure change with placebo (p less than 0.05). Doxazosin therapy led to a small increase in weight (p less than 0.05). It was also associated with a statistically insignificant decrease in renal vascular resistance (568 dynes s/cm5) so that renal blood flow and creatinine clearance did not change. Doxazosin increased renin levels acutely and norepinephrine levels with 6-week treatment, but these changes were not significantly different from placebo. Norepinephrine clearance, measured after a 120-minute infusion of 3H norepinephrine, did not change. Heart rate increased acutely after doxazosin administration, but returned to baseline during 6-week therapy. Blood pressure, measured hourly for 14 hours after treatment, was consistently decreased in all patients. Doxazosin taken once daily lowers blood pressure without affecting renal blood flow or heart rate.
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PMID:Effects of alpha 1 inhibition on renal blood flow and sympathetic nervous activity in systemic hypertension. 288 58

The antihypertensive and lipid effects of doxazosin and atenolol were compared in a 10-week, double-blind, parallel, placebo-controlled study. The 129 adults enrolled had mild to moderate hypertension (average supine diastolic blood pressures for doxazosin, atenolol and placebo were 100.6, 101.0 and 99.7 mm Hg, respectively). Patients were randomly assigned to treatment with doxazosin, 1 to 16 mg daily, atenolol, 50 to 100 mg daily or placebo. Among 114 patients included in the efficacy analysis, standing blood pressure (systolic/diastolic) changed by -13/-11 mm Hg with doxazosin (n = 37), -12/-12 mm Hg with atenolol (n = 39) and +1/-1 mm Hg with placebo (n = 38). Mean reductions in blood pressure for doxazosin and atenolol were significantly greater than those for placebo (p less than 0.01), although no statistically significant differences between the active agents were noted. Serum lipid measurements were evaluable for 116 patients, and the 38 doxazosin-treated patients in this group experienced reductions in total cholesterol, total triglyceride and very low density lipoprotein cholesterol levels. Both doxazosin and atenolol demonstrated comparable acceptance profiles. Doxazosin is an effective hypotensive agent with beneficial effects on serum lipid levels.
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PMID:A double-blind parallel trial to assess the efficacy of doxazosin, atenolol and placebo in patients with mild to moderate systemic hypertension. 288 59

Since it is not known for certain which alpha-adrenergic receptors mediate renal vasoconstriction in human essential hypertension, we infused either doxazosin (n = 7) or yohimbine (n = 7) into the renal arteries of hypertensive subjects immediately prior to diagnostic angiography. Both agents caused an increment in renal blood flow as assessed with the xenon-washout technique. Doxazosin increased renal flow from 342 +/- 36 to 360 +/- 55 ml/min per 100 g (0.05 less than p less than 0.10). Yohimbine enhanced flow from 380 +/- 41 to 485 +/- 63 ml/min per 100 g (p less than 0.01). The effect of yohimbine was significantly greater than that of doxazosin. In a control group (n = 7) receiving only saline, no changes in renal blood flow occurred. Doxazosin enhanced renin secretion in the kidney by 10 +/- 4% over levels in controls (0.05 less than p less than 0.10), whereas yohimbine increased renin release by 80 +/- 23% (p less than 0.01). The latter increase was apparently not due to alterations in flow alone, since the arteriovenous gradient for renin also widened. We conclude that in resting conditions, neurogenic vascular tone in the kidney depends mainly upon activation of alpha 2-adrenergic receptors. Moreover, these receptors exert a tonic inhibitory influence on renin release.
Hypertension 1987 Jun
PMID:Role of alpha 1- and alpha 2-adrenergic receptors in the human hypertensive kidney. 288 75


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