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

A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition. In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated.
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PMID:Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. 1 Jul 30

The mechanisms of action, clinical use and untoward reactions of the beta-adrenergic blocking drugs, with particular attention to the role of these agents in the treatment of hypertension, are reviewed. Specific topics covered include the effect of beta-adrenergic blockade on the heart, renin secretion and the central nervous system; the efficacy and pharmacokinetics of beta-blocking agents; combinations with other drugs; patient acceptance and advantages; and toxicity and side effects. It is concluded that, with proper dosage titration, most hypertensive patients could probably be controlled on beta blockers alone or in combination with a diuretic.
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PMID:Beta blockers in hypertension: a review. 1 87

The renin-angiotensin system appears to play a major role in the regulation of sodium excretion and fluid intake in a wide variety of animal species from mammals to teleosts. In mammals the system has evolved further importance in terms of blood pressure homeostasis. This hormonal system in all species appears to involve a serum protein prohormone, angiotensinogen, a proteolytic enzyme, renin, and angiotensin I, the decapeptide product of the reaction between renin and angiotensinogen. The importance of this system to the organism appears to correlate directly with the necessity to conserve sodium while an abnormality of this process may underlie the development of hypertension in man. As the starting point of the system, angiotensinogen assumes special importance as a possible index of evolutionary development. In addition, it has been known for many years that human (viz. primate) angiotensinogen differs from that found in other mammals in its inability to be a substrate for animal renins while animal angiotensinogens readily react with human renin. Thus, the enzymatic specificity appears to reside with the prohormone. The biochemical basis for this difference is unresolved due primarily to the lack of purified human angiotensinogen. In this paper we describe methods for the purification of human angiotensinogen which have direct applicability to animal angiotensinogens. Our approach utilizes ammonium sulfate precipitation, Sephadex G-150 chromatography, multiple isoelectric focusing, and concanavalin A-Sepharose affinity chromatography. With the availability of highly purified human angiotensinogen we compared the molecular weights, heterogeneity, isoelectric points, and thermal lability of hog, rabbit, and human angiotensinogen in order to define the biochemical basis of the species variation in renin reactivity...
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PMID:Human angiotensinogen. Purification partial characterization, and a comparison with animal prohormones. 1 60

Only recently approved for use in the treatment of hypertension in the US, the beta-adrenergic receptor blocking compound propranolol has been used elsewhere for this purpose since 1964. The exact mechanisms to explain why and how "beta-blocking drugs" reduce arterial pressure are not known with certainty, but possible explanations include: (1) "resetting" of the baroreceptors, (2) reduction of cardiac output, (3) adaptation of circulation ("autoregulation"), (4) inhibition of renin release, (5) central nervous system effects, (6) possible antihypertensive metabolites, and (7) other unknown mechanisms or a combination of known mechanisms. Propranolol alone has been demonstrated to be extremely effective in reducing arterial pressure. In addition, the combination of propranolol and vasodilator and diuretic drugs would be expected to reduce vascular resistance without reflexive cardiac stimulation and with prevention of sodium and fluid retention.
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PMID:Pathophysiology of propranolol in hypertension. 1 2

Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%) or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall in two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of betablocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, betablockers normalized blood pressure (less than or equal to 95 mm Hg diastolic) in three-quarters of the younger-than-40-year-olds, in about half of those 40-60 years of age but in only 20% of those over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state whereas those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the betablockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, although not exclusively, to renin suppression.
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PMID:Renin and age as determinants of a predominantly betablocker-based antihypertensive drug program. 1 85

The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade.
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PMID:The essential action of propranolol in hypertension. 1 98

There is good evidence from many sources that beta-adrenoreceptor blockade is an effective form of therapy in mild, moderate and severe hypertension either alone or in combination with other antihypertensive agents. Although a number os such beta blocking compounds are now available, they appear to have a hypotensive effect of approximately equal magnitude. This hypotensive effect is obtained in both the supine and standing positions thus avoiding postural hypotension. The maximum hypotensive effect may take some time to become apparent. Despite considerable work the mode of action remains uncertain, reduction in cardiac output, resetting of baroreceptors, reduction in plasma renin and a central nervous system effect have been suggested but remain unproved. There is evidence to suggest that these compounds can control, to some degree, the surges in blood pressure resulting from either mental or physical stress. A low incidence of serious side effects has been reported by many workers. Only the long-term use of these compounds in comparison with other antihypertensive agents will determine their place in the management of hypertension.
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PMID:Beta-adrenoreceptor blockade in hypertension. 1 2

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.
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PMID:Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension. 1 4

From analyses of the effectiveness of beta-blocker monotherapy in relation to the patient's age and to pre-treatment renin determinations an antihypertensive drug program is proposed in which beta-blockers form the cornerstone. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older pateients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of beta-blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta-blockers normalized blood pressure (larger than or equal to 95 mmHg diastolic) in three-quarters of the younger than 40-year-olds, in about half of those aged 40--60 years, but in only 20% of those aged over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the beta-blockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, though not exclusively, to renin suppression.
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PMID:A beta-blocker-based antihypertensive drug program guided by age and renin. 1 22

Complications of hypertension are by far the greatese preventable public health problem in many of the developed countries of the world. Pharmacologic interventions which primarily involve drug interactions are the generally available and effective means of preventing or delaying these hypertensive complications. Mechanisms of beneficial antihypertensive drug interactions involve simultaneous reduction or control of blood volume (diuretic agents) and decrease of peripheral resistance. Reduction of peripheral resistance without producing intolerable side effects has recetnly been achieved by a complex drug interaction. This interaction involves simultaneous vasodilation and inhibition by beta-adrenergic blocking agents of reflex activation of the renin-angiotensin axis. Clonidine, by effects similar to propranolol, can substitute for propranolol in some patients, or add to the beneficial effects of this important drug interaction.
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PMID:Additive effect of beta-adrenergic blockers in combination with vasodilators in lowering blood pressure. 1 26


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