Controlled Trial of Propranolol in Hypertension

Zacharias, Farouk; Cowen, Kay J.

doi:10.1136/bmj.1.5694.471

Cited by 91 publications

(27 citation statements)

References 9 publications

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“…The mechanism of action of f-adrenoceptor antagonists in the treatment of essential hypertension is not clear (Dorph & Binder, 1969;Prichard & Gillam, 1969;Tibblin & Ablad, 1969;Zacharias & Cowan, 1970;Thorpe, 1972 (1973) reported that dibutyryl cyclic AMP and theophylline increase the release of noradrenaline elicited by nerve stimulation in the guinea-pig vas deferens. In addition, monobutyryl cyclic AMP and several phosphodiesterase inhibitors increase transmitter release in the perfused cat spleen (Cubeddu, Weiner & Langer, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, there is little information about the effects of (-adrenoceptor agonists and antagonists on transmitter released by nerve stimulation, although propranolol and other (3-adrenoceptor blocking agents are used in the treatment of hypertension (Dorph & Binder, 1969;Prichard & Gillam, 1969;Tibblin & Ablad, 1969;Zacharias & Cowan, 1970;Thorpe, 1972) and it appears that inhibition of release of adrenergic transmitter may contribute to their hypotensive effect (Mylecharane & Raper, 1970;Eliash & Weinstock, 1971).…”

Section: Introductionmentioning

confidence: 99%

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POSSIBLE ROLE OF a Β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH a POSITIVE FEED‐BACK MECHANISM

Adler‐Graschinsky

Langer

1975

British J Pharmacology

328

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The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea‐pig isolated atria. Isoprenaline (1.2 × 10−8) increased while propranolol (1.0 × 10‐7 M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 × 10‐6 M), which increased by approximately three‐fold the overflow of [3 H] ‐noradrenaline elicited by nerve stimulation. Neuronal accumulation of tritiated noradrenaline in guinea‐pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentrations employed in this study. Isoprenaline (1.2 × 10‐8 M) induced a positive chronotropic effect of about 80% of the maximum. On the other hand, propranolol produced a shift to the right in the frequency‐response curve to nerve stimulation and in the concentration‐response curve to exogenous noradrenaline in guinea‐pig atria. In the isolated nictitating membrane of the cat, the frequency‐response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 × 10−6 m of N,‐2‐(2,6‐dimethylphenoxy)propyl‐N,N,N ‐trimethylammonium (β‐methyl‐TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor β‐methyl‐TM 10 affected responses to exogenous noradrenaline. The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed‐back mechanism for noradrenaline release by nerve stimulation mediated via α‐adrenoceptors a positive feed‐back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic β‐adrenoceptors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

POSSIBLE ROLE OF a Β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH a POSITIVE FEED‐BACK MECHANISM

Adler‐Graschinsky

Langer

1975

British J Pharmacology

328

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“…been used in the treatment of hypertension by virtue of their action in altering cardiac function (Prichard & Gillam, 1969;Zacharias & Cowen, 1970). In clinical use the onset of the blood pressure fall with propranolol is delayed and treatment is associated with an increase in vasoconstrictor tone.…”

Section: Pmentioning

confidence: 99%

PROCEEDINGS OF THE BRITISH PHARMACOLOGICAL SOCIETY, 8TH‐9TH‐10TH July, 1970

1970

British J Pharmacology

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“…Group II Propranolol It was with propranolol that the value of ,B-adrenoceptor blocking agents in hypertension has been established (Prichard & Gillam, 1964Baczko, Dabrowska & Wocial, 1967;Frohlich, Tarazi, Dustan & Page, 1968;Tewari & Grant, 1968;Zacharias & Cowen, 1970;Karlberg & Hornkvist, 1971;Zacharias, Cowen, Vickers & Wall, 1972). Prichard & Gillam (1969) reported the first large study, 109 patients treated for up to 4 years.…”

Section: Introductionmentioning

confidence: 99%

The second Lilly Prize Lecture, University of Newcastle, July 1977. beta‐Adrenergic receptor blockade in hypertension, past, present and future.

Prichard¹

1978

Brit J Clinical Pharma

102

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All beta‐adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta‐adrenoceptor blocking drugs have been reported which also possess alpha‐adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta‐adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta‐adrenoceptor blocking drugs. The non‐selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I‐IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta‐adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub‐divided into groups I‐IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta‐adrenergic receptor blocking drugs which in addition have alpha‐ adrenergic receptor blocking properties (Division III).

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Controlled Trial of Propranolol in Hypertension

Cited by 91 publications

References 9 publications

POSSIBLE ROLE OF a Β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH a POSITIVE FEED‐BACK MECHANISM

POSSIBLE ROLE OF a Β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH a POSITIVE FEED‐BACK MECHANISM

PROCEEDINGS OF THE BRITISH PHARMACOLOGICAL SOCIETY, 8TH‐9TH‐10TH July, 1970

The second Lilly Prize Lecture, University of Newcastle, July 1977. beta‐Adrenergic receptor blockade in hypertension, past, present and future.

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