Central Nervous Actions of β-Adrenoreceptor Antagonists

Conway, James; Greenwood, D. T.; Middlemiss, Derek N.

doi:10.1042/cs0540119

Cited by 29 publications

(17 citation statements)

References 155 publications

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“…A persuasive line of evidence that the renin system might be actively involved in essential hypertension emerged from a study by Bflhler with our group 8 in which we demonstrated that the beta-adrenergic blocking drug, propranolol, lowered BP in proportion to the height of the control renin level and also in proportion to the degree to which renin levels were reduced by the beta blocker. The study showed that not only was the beta-adrenergic receptor blocker, propranolol, most effective in lowering BP in highrenin human essential hypertension, but, conversely, in low-renin forms it usually had no effect or was even pressor.…”

Section: Proof Of Renin Participation In Essential Hypertensionmentioning

confidence: 99%

“…This cardiac theory must then invoke some secondary mechanism, related to variable reactive changes in peripheral resistance consequent to the reduction in cardiac output. 8 -" However, such postulated reactive changes in arteriolar tone would still have to be shown independent of changes in resistance produced by the induced reduction of angiotensin II levels.…”

Section: Proof Of Renin Participation In Essential Hypertensionmentioning

confidence: 99%

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Captopril compared with other antirenin system agents in hypertensive patients: its triphasic effects on blood pressure and its use to identify and treat the renin factor.

Laragh¹,

Case²,

Atlas³

et al. 1980

Hypertension

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SUMMARY Four different pharmacologlc probes (propranolol, saralasin, teprotide, and captopril) hare exposed and characterized the active participation of the renin system in sustaining the derated blood pressure (BP) of most essential hypertension (I.e., the high and "normal" renin forms). Research indicates that renin measurements can be used to predict the effects of these drags on BP, since control plasma renin actirity levels correlate closely with reductions in pressure. Therefore, the renin assay provides a reliable estimate of angiotensin-mediated rasoconstriction, the normalcy of which is gauged by relating it to the urinary sodium excretion, an index of intake and balance. The effects of continued oral administration of captopril closely resemble those previously described with the Intravenously administered nonapeptide-converting enzyme inhibitor, teprotide. Correlations between the induced antibypertensive effect and control plasma renin levels for 89 and 100 different patients receiving either teprotide or captopril alone were 0.82 and 0.89 respectively. The fact that captopril, like the other three antirenln-system drugs, was inactive in low renin states, including in primary aldosteronism and anephric patients, verifies the view that its main antibypertensive action is mediated via renin system blockade.The BP response of untreated patients 90 minutes after an oral dose of captopril can be predictive of its long-term effectiveness. Of practical relevance is a transient rebound of BP observed in the first few days of continuous therapy, with pressures sometimes returning near control levels. This rebound usually subsides by 7 days. Captopril produces continued suppression of the renin system as evidenced by reduced plasma aldosterone levels. But the system retains a capacity to override drag blockade in response to physiologic stimuli. The great potency with specificity of captopril is expressed by its correction of hypertension with few side effects. The cumulative experience with this and earlier pharmacologic probes has opened the door to new approaches in diagnosis and therapy based on analysis of renin system behavior. It also points the way to new research to determine why the renin system so often participates in essential hypertension and to define other pressor factors that might operate when renin and sodium factors are absent or blocked. . using the new antihypertensive agent, captopril, system contribution to the BP level is helpful for exand compare its effects with those we have obposing both renin-system and nonrenin system served using other agents to block activity of the renin mechanisms involved in the particular hypertension, system. Our research is based on the concept that the If one views the renin system as a long-term renin system maintains and defends arterial BP while regulator of the BP level, then it follows that stimuli also regulating sodium and potassium balance. We that tend to lower pressure will activate the system reason that if, in fact, the renin system is a tru...

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Section: Proof Of Renin Participation In Essential Hypertensionmentioning

confidence: 99%

Section: Proof Of Renin Participation In Essential Hypertensionmentioning

confidence: 99%

Captopril compared with other antirenin system agents in hypertensive patients: its triphasic effects on blood pressure and its use to identify and treat the renin factor.

Laragh¹,

Case²,

Atlas³

et al. 1980

Hypertension

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show abstract

“…The tabulated results were calculated directly from the equilibrium concentration of the drug on each Although some,B-adrenoceptor blocking drugs such as propranolol have been shown to be effective in the treatment of a variety of central nervous system disorders such as schizophrenia, anxiety, tremor (Conway, Greenwood & Middlemiss, 1978), whether their mechanism of action is centrally or peripherally mediated is not resolved. Propranolol is known to penetrate the blood-bralff barrier in animals and man (Day, Hemsworth & Street, 1977;Myers, Lewis, Reid & Dollery, 1975).…”

mentioning

confidence: 99%

Protein binding of atenolol and propranolol to human serum albumin and in human plasma [proceedings]

Barber¹,

Hawksworth²,

Kitteringham³

et al. 1978

Brit J Clinical Pharma

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“…Although some,B-adrenoceptor blocking drugs such as propranolol have been shown to be effective in the treatment of a variety of central nervous system disorders such as schizophrenia, anxiety, tremor (Conway, Greenwood & Middlemiss, 1978), whether their mechanism of action is centrally or peripherally mediated is not resolved. Propranolol is known to penetrate the blood-bralff barrier in animals and man (Day, Hemsworth & Street, 1977;Myers, Lewis, Reid & Dollery, 1975).…”

Section: Pmentioning

confidence: 99%