ACTIONS OF BRETYLIUM AND GUANETHIDINE ON THE UPTAKE AND RELEASE OF [<sup>3</sup>H]‐NORADRENAUNE

Hertting, G.; Axelrod, Julius; Patrick, Raymond W.

doi:10.1111/j.1476-5381.1962.tb01159.x

Cited by 89 publications

(29 citation statements)

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“…Decreased tissue uptake might therefore account for the increased amounts of adrenaline and noradrenaline found after the injection of guanethidine and bretylium, for Hertting, Axelrod & Patrick (1962) showed that in the rat bretylium and guanethidine decreased tissue uptake of [3H]-noradrenaline. Bhagat & Shideman (1963) disagree with this for bretylium but agree with the finding for guanethidine.…”

Section: Discussionmentioning

confidence: 99%

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

Abbs

1966

British Journal of Pharmacology and Chemotherapy

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Section: Discussionmentioning

confidence: 99%

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

Abbs

1966

British Journal of Pharmacology and Chemotherapy

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“…However, intravenous infusion of norepinephrine and serotonin to reserpine pretreated rabbits did not correct the blood pressure response to ST-155. Guanethidine interferes with a release of norepinephrine from adrenergic nerve terminals due to tyramine, nerve stimulation (10) and reserpine (12). In rats the amount of norepine phrine is depleted by about 80% following pretreatment with guanethidine for 6 to 24 hours (11), whereas the amount of tissue serotonin is not depleted after 6 hours (11).,…”

Section: Discussionmentioning

confidence: 99%

The Mode of Hypotensive Actions of 2-(2,6-Dighlorophenyl-L-Amino)-Imidazoline in the Rabbit

Toda

Fukuda

Shimamoto

1969

Japanese Journal of Pharmacology

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A new antihypertensive drug, 2-(2,6-dichlorophenyl-l-amino)-imidazoline hydrochloride (ST-155) (1-5) which structurally resembles tolazoline has been reported to possess no adrenergic alpha-receptor blocking action as does tolazoline (1). Clinical trials show that ST-155 effectively reduces the blood pressure level of hypertensive patients who have not responded to any other antihypertensive drugs (2). Peripheral vascular resistance is decreased (2) and cardiac work is considerably reduced (4) in correspondence with the manifestation of a blood pressure fall in hypertensive patients.Nayler et al. (6) have postulated that the beta-adrenergic mechanism is involved in the hypotensive action of ST-155 from results observed in dog heart-lung bypass prepa rations (7) in which the hypotensive action is blocked by propranolol and pentolinium. In the present experiments the mode of hypotensive actions of ST-155 was investigated more extensively on anesthetized rabbits, since this species always exhibited the marked and consistent depressor response to the drug. The results preclude the participation of the beta-adrenergic mechanism in hypotensive action. Actions of ST-155 on central and peripheral cardiovascular mechanisms were postulated to be responsible for its hypotensive action in anesthetized rabbits. METHODSEight cats of both sexes, weighing 3 to 4.5 kg, and 51 albino rabbits of both sexes, weighing 2 to 2.5 kg, were used. In situ experimentsCats and rabbits were anesthetized with intraperitoneal injection of pentobarbital sodium in an initial dose of 30 to 40 mg/kg. Supplemental doses of the anesthetic drug were injected intravenously from time to time as required in order that a constant anesthetic stage was maintained. Anesthesia was carefully induced to animals pretreated with reserpine with much smaller doses of pentobarbital sodium (15 to 20 mg/kg). The mean blood pressure of the left carotid artery was recorded on a smoked paper via an arterial cannula and a mercury manometer. Spontaneous respiration was recorded on a smoked paper by means of rubber tambour connected to a tracheal cannula, simulta

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“…It has been established that sodium ions play an essential role in the uptake, retention and storage of noradrenaline in adrenergic nerve endings (Iversen & Kravitz, 1966;Gillis & Paton, 1967;Kirpekar & Wakade, 1968;Bogdanski & Brodie, 1969). The major mechanism involved in this increase in the output of noradrenaline seems to be an inhibition of the retention rather than that of the reuptake, because guanethidine, a potent inhibitor of the uptake (Hertting, Axelrod & Patrick, 1962), did not potentiate the efflux induced by low sodium. Garcia & Kirpekar (1973) demonstrated that the various procedures which are known to inhibit Na+, K+-activated ATPase or the sodium potassium pump, induce the efflux of noradrenaline.…”

Section: Resultsmentioning

confidence: 99%

Prevention by Guanethidine Analogues of Output of Noradrenaline Induced by Sodium Reduction in Rabbit Ventricular Slices

Hosotani

Misu

1978

British J Pharmacology

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The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mm ethylene glycol‐bis(aminoethyl‐ether)N,N,N′,N′ tetra‐acetic acid (EGTA) or by an increase in the calcium concentration to 10 mm 30 min before sodium deprivation. Guanethidine 4 × 10−6 and 4 × 10−5m and 4–7‐exo‐methylene‐hexahydroisoindoline‐ethyl guanidine (No. 865‐123) 4 × 10−5 to 8 × 10−4m inhibited, in a dose‐dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mm, while guanethidine 8 × 10−5m and high doses of bretylium produced no inhibition: the latter two released noradrenaline. The inhibitory actions of guanethidine 4 × 10−5m and No. 865‐123 4 × 10−4m were prevented by tetracaine 3.3 × 10−4m, which per se did not modify the output of noradrenaline induced by 18 mm sodium. Accumulation of guanethidine and No. 865‐123 in ventricular slices was greater than that noted in striated muscle slices and was dose‐, time‐ and temperature‐dependent. Tetracaine 3.3 × 10−4m did not prevent the accumulation of guanethidine 4 × 10−5m and No. 865‐123 1.1 × 10−6 to 4 × 10−4m. The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.

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ACTIONS OF BRETYLIUM AND GUANETHIDINE ON THE UPTAKE AND RELEASE OF [³H]‐NORADRENAUNE

Abstract: The effect of bretylium and guanethidine has been studied on the uptake and the spontaneous and reserpine-induced release of [3H]-noradrenaline in the rat heart and in the splenic nerve endings of the cat. Bretylium and guanethidine

Cited by 89 publications

References 9 publications

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

The Mode of Hypotensive Actions of 2-(2,6-Dighlorophenyl-L-Amino)-Imidazoline in the Rabbit

Prevention by Guanethidine Analogues of Output of Noradrenaline Induced by Sodium Reduction in Rabbit Ventricular Slices

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ACTIONS OF BRETYLIUM AND GUANETHIDINE ON THE UPTAKE AND RELEASE OF [3H]‐NORADRENAUNE

Abstract: The effect of bretylium and guanethidine has been studied on the uptake and the spontaneous and reserpine-induced release of [3H]-noradrenaline in the rat heart and in the splenic nerve endings of the cat. Bretylium and guanethidine

Cited by 89 publications

References 9 publications

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

The Release of Catechol Amines by Choline 2,6‐xylyl Ether, Bretylium and Guanethidine

The Mode of Hypotensive Actions of 2-(2,6-Dighlorophenyl-L-Amino)-Imidazoline in the Rabbit

Prevention by Guanethidine Analogues of Output of Noradrenaline Induced by Sodium Reduction in Rabbit Ventricular Slices

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ACTIONS OF BRETYLIUM AND GUANETHIDINE ON THE UPTAKE AND RELEASE OF [³H]‐NORADRENAUNE