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

Many studies have suggested that alpha-adrenergic receptors on vascular smooth muscle are heterogeneous and that both alpha 1- and alpha 2-adrenergic receptors can cause vasoconstriction when stimulated. We explored this hypothesis in normal humans by comparing the capacity of yohimbine, an alpha 2-adrenergic receptor antagonist, and prazosin, an alpha 1-adrenergic receptor agonist, with differentially blocked pressor responses to phenylephrine, an alpha 1-adrenergic receptor agonist, and epinephrine, a nonselective alpha-agonist. We studied these responses in normal male volunteers who had been pretreated with propranolol (80 mg orally every 8 hours for 5 days) to obviate stimulation of beta-receptors by either agonist. We found differential effects of the antagonists on responses to the two agonists. Yohimbine induced a 3.1-fold (+/- 0.5) shift in the dose of epinephrine, which raised blood pressure 25 mm Hg, and only a 1.9-fold (+/- 0.2) shift in the response to phenylephrine (p less than 0.01). Prazosin induced a 2.4-fold (+/- 0.5) shift in the responses to epinephrine and a 4.5-fold (+/- 1.2) shift in the response to phenylephrine (p less than 0.05). These data are consistent with the notion that alpha-adrenergic receptors in the human vasculature are not homogeneous, but rather may be subdivided into at least two subtypes, one resembling alpha 1-adrenergic receptors and the other resembling alpha 2-adrenergic receptors.
Hypertension
PMID:Evidence for the existence of vascular alpha 2-adrenergic receptors in humans. 608 19

The effects of oral administration of 2 mg prazosin on several metabolic and endocrine variables were evaluated in 12 patients with hypertension (6 with normal and 6 with abnormal glucose tolerance). Prazosin was followed by a rise in plasma glucose and serum free fatty acids (FFA) in both normal and diabetic subjects; there was a trend upward in serum albumin (IRI), but growth hormone (GH), prolactin (PRL), and gastrin did not change. Although these results are in general agreement with metabolic effects of other alpha adrenergic blockers already reported, the rise in plasma glucose is at variance with studies performed with phentolamine.
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PMID:Metabolic effects of prazosin. 610

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.
Hypertension
PMID:Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. 610 28

Forty-seven consecutive hypertensive patients, 27 of whom were inadequately controlled on previous therapy, were included in a general-practice study using prazosin hydrochloride as anti-hypertensive therapy. Eleven (23 percent) had their hypertension controlled by prazosin alone, increasing to 68 percent with the addition of a diuretic, and to 87 percent by adding a beta blocker with or without a diuretic. The range of dosage varied widely and the side effects, although frequent, were not serious. Prazosin is considered to be a useful anti-hypertensive agent especially in combination with thiazides and/or beta blockers.
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PMID:Prazosin in general practice. 611 25

Prazosin was the result of an attempt to find a directly acting vasodilator drug with little or no effect on cardiac output, renin and salt and water metabolism. Clinical studies confirmed that these desirable features were possessed by prazosin in spite of an apparently peripheral mode of action and thus prazosin contrasted strongly with all other agents of this type. Prazosin differs from the classical alpha-adrenoceptor antagonists in possessing marked selectivity for alpha 1-adrenoceptors as opposed to alpha 2-adrenoceptors. This ensures the preservation of the local feedback control of the release of noradrenergic transmitter by the pre-junctional alpha 2-adrenoceptors. This fact appears to be responsible for the therapeutic success of prazosin and why prazosin is the first alpha-adrenoceptor blocking drug to be effective in the treatment of hypertension. The marked selectivity for alpha 1-adrenoceptors makes prazosin invaluable as a research tool, especially as a radioligand for the identification of alpha 1-adrenoceptors.
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PMID:The pharmacology of prazosin, an alpha 1-adrenoceptor antagonist and the basis for its use in the treatment of essential hypertension. 612 21

Prazosin, an orally active alpha-1 selective adrenergic antagonist, has been of value in treating patients with hypertension and congestive heart failure. In contrast to non-subtype-selective alpha-adrenergic antagonists and direct-acting vasodilators, prazosin's hypotensive action is accompanied by little or no increase in heart, rate, plasma renin, or plasma norepinephrine. Prazosin is a versatile drug that may be used alone or in combination to treat mild, moderate, or severe hypertension. The antihypertensive effect is sustained, and may increase during long-term therapy. The major side effect, postural hypotension after the first drug administration, is related to drug dose and intravascular volume depletion. Other side effects are mild and seldom limit therapy. In patients with congestive heart failure, prazosin results in balanced venous and arterial dilation, similar to that produced by nitroprusside. Attenuation of some or all of prazosin's initial hemodynamic effects has been seen during multiple short-term administrations. However, chronic studies have shown sustained symptomatic and hemodynamic improvement during long-term administration; initial hemodynamic attenuation may be transient or partial, and does not preclude long-term effectiveness, particularly during exercise. Preliminary studies indicate that prazosin may also be effective in treating patients with peripheral vasospasm due to Raynaud's phenomenon or ergotamine overdose.
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PMID:Alpha-adrenergic receptor blockade with prazosin. Consideration of hypertension, heart failure, and potential new applications. 612 97

The Hypertension Detection and Follow-up Program (HDFP) first demonstrated that treatment of patients with mild hypertension (90 to 104 mm Hg diastolic) could reduce morbidity and mortality in coronary heart disease (CHD). Previous studies had already shown the beneficial effect of blood pressure reduction on renal disease, heart failure, and cerebrovascular disease. When uncontrolled, mild hypertension in the patient with renal disease will lead to further deterioration of renal function. To prevent this and other complications (such as atherosclerosis) of hypertension, whether primary or secondary, one should place these patients on antihypertensive therapy. However, standard stepped-care therapy with diuretic drugs and beta-blocking agents is now under reevaluation in view of the potential adverse effect of these agents on serum lipids and renal function. Beta-blocking drugs, furthermore, tend to increase peripheral resistance, a hemodynamic effect opposite to that desired in these patients. Other drugs, acting centrally or peripherally on the nervous system, also have some undesirable features in addition to troublesome side effects. Prazosin, a vasodilator and effective antihypertensive agent with a different mechanism of action, has no adverse action on lipids and renal function, lowers peripheral resistance, and does not cause many of the side effects that limit use of the other drugs. It therefore appears to be a good choice for initial therapy in mild to moderate hypertension with associated renal insufficiency.
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PMID:Treating the patient with mild hypertension and renal insufficiency. 613 5

Although hypertension is a well-established coronary risk factor, controlled, randomized hypertension drug trials have failed to show a definite preventive effect on the incidence of coronary heart disease. Possible adverse metabolic effects, particularly on blood lipids, of some commonly used antihypertensive drugs have been investigated. During the Oslo Study on the treatment of mild hypertension, which was not specifically designed to study the effect on lipids, a decrease in serum high-density lipoprotein cholesterol and an increase in serum triglycerides was observed with a combination of propranolol and hydrochlorothiazide. Therefore, special trials were designed specifically to study the effect of various antihypertensive drugs on blood lipids. Propranolol reduced serum high-density lipoprotein cholesterol (13 percent) and the cholesterol ratio [high-density lipoprotein cholesterol:(low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol)] by 15 percent and increased total serum triglycerides by 24 percent. Prazosin significantly (p less than 0.01) reduced total serum cholesterol, (9 percent) low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol (10 percent), and total triglycerides (16 percent), whereas the cholesterol ratio increased by 7 percent. The reduction in high-density lipoprotein cholesterol with propranolol plus prazosin was less than that with propranolol alone. Pindolol (with a high sympathomimetic activity) did not significantly change total cholesterol, low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or total triglycerides. Prazosin plus pindolol reduced serum low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol. The observed reductions in serum high-density lipoprotein cholesterol and the cholesterol ratio with oxprenolol were 11.5 percent and 13.7 percent, respectively, and with atenolol 16.7 percent and 19.2 percent, respectively, whereas total serum triglycerides were increased by 14.9 percent with oxprenolol and 17.9 percent with atenolol. Data provided by other European groups comparing the effect of antihypertensive treatment on lipid metabolism are also reviewed.
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PMID:Effect of alpha- and beta-blocker therapy on blood lipids: European experience. 614 44

Pharmacological treatment of hypertension can cause clinically significant alterations in endocrine function through effects on glucose homeostasis, thyroid and parathyroid hormones, adrenal steroid metabolism and reproductive/pituitary physiology. Long term use of thiazide diuretics causes deterioration in glucose tolerance, probably secondary to potassium depletion. Hypoglycaemic complications of beta-blockers (mainly the non-selective compounds) can be dramatic, especially in type I diabetics. Clonidine, diazoxide and calcium antagonists have all been associated with deterioration in glucose tolerance and their long term use should be avoided in type II diabetics if possible. Propranolol lowers T3 levels by decreasing the conversion of T4 to T3. Prazosin causes elevations in T4 and thyroid-stimulating hormone, while sodium nitroprusside use may result in hypothyroidism. Numerous agents are associated with sexual dysfunction, including methyldopa, reserpine, clonidine and spironolactone. Thiazide diuretics may cause hypercalcaemia, particularly in patients with hyperparathyroidism, by decreasing urinary calcium as well as directly influencing bone and gut calcium handling. Conversely, propranolol may decrease circulating parathyroid hormone levels and correct the hypercalcaemia seen in hyperparathyroidism. Awareness of drug-induced changes in endocrine function will facilitate the rational management of the hypertensive patient.
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PMID:Effects of antihypertensive drugs on endocrine function. 614 2

Combined use of prazosin and beta-blockers in a hypertension clinic over a 3-year period was surveyed by means of a computerized record system. Of the 1,250 patients in the clinic, 171 (14%) had been treated with this combination for periods averaging 17 months. Prazosin was administered with a beta 1-selective beta-blocker in 94 cases and with a beta 1 + beta 2-blocker in 100 cases; 23 patients had received treatment with both combinations. Diuretics were given in 86% of cases and other antihypertensive drugs in 19%. The population treated had a high incidence of severe hypertension, with initial diastolic pressure greater than 120 mm Hg in 38% and between 100 and 120 mm Hg in 50%. The percentage of patients with diastolic pressure less than 100 mm Hg was 12% initially and 79% at the end of the treatment period. Side effects necessitated withdrawal of therapy in 35 cases. These were referable in 19 cases to prazosin and in 16 to beta-blockers. Prazosin was found to be more effective in lowering blood pressure in combination with beta 1-blockers than with beta 1 + beta 2-blockers, although there were fewer severe side effects with beta 1-blockers.
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PMID:Combined use of prazosin and beta-blockers in hypertension. 617 35


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