The action of reserpine on the peripheral sympathetic system

Abstract

Reserpine causes the release of 5-hydroxytryptamine (5-HT) from all tissues in which it is normally stored. This release is shown by a fall in the tissue concentration of 5-HT and by an increase in its urinary metabolites (Pletscher, Shore & Brodie, 1955;Shore, Silver & Brodie, 1955). That reserpine may also lower the concentration of catecholamines in tissues was shown by experiments (Holzbauer & Vogt, 1956) in which the disappearance of noradrenaline from the hypothalamus was demonstrated in cats injected with small doses of reserpine (0-4 mg/kg). This depletion, however, did not occur in all organs, the denervated, in contrast to the innervated, adrenal medulla remaining unaffected by this dose of the drug.It is tempting to try to correlate the effects on behaviour and responsiveness produced by reserpine with the loss of 5-HT and noradrenaline from the brain. The tendency has been to attribute not only the sedation, but also such signs as the fall in blood pressure, the miosis and the relaxation of the nictitating membrane to central changes alone. Although all these phenomena might be due to central causes, they could also be produced, at least partly, by disturbances in the peripheral sympathetic system. Failure of another sympathetic mechanism after reserpine was described by G. M. Everett who observed (personal communication, and Everett, Toman & Smith, 1957) that cold did not produce pilo-erection in mice injected with reserpine. This failure, too, might be due to a central or to a peripheral derangement, or to both.The aim of the present paper is to determine the effect of reserpine on the peripheral sympathetic tissues: the investigation, abstracts of which have been published (Muscholl & Vogt, 1957 a, b), deals with the loss of transmitter and the damage to function produced by reserpine in adrenergic neurones. In preliminary experiments the normal range of concentrations of adrenaline and noradrenaline in various parts of the sympathetic system was established.

STUDIES ON THE ANTAGONISM BETWEEN THE OPTICAL ISOMERS OF N‐(1‐PHENYLETHYL)GUANIDINE

“…It is generally accepted that sympathetic blockade by reserpine results from loss of the neurotransmitter, noradrenaline, from sympathetic nerve endings (Carlsson, Rosengren, Bertler & Nilsson, 1957;Muscholl & Vogt, 1958). This is not so for guanethidine, which produces sympathetic blockade before extensive depletion of tissue noradrenaline has occurred (Cass & Spriggs, 1961;Gaffney, Chidsey & Braunwald, 1963).…”

Depletion and Replacement of the Adrenaline and Noradrenaline Contents of the Rat Adrenal Gland, Following Treatment With Reserpine

“…In the brain of rabbits (Brodie, Olin, Kuntzman & Shore, 1957) a maximum depletion of 90% occurred 4 hr after 5 mg/kg intravenously of reserpine. This was also the time at which maximum depletion occurred in the cervical and solar ganglia of the rabbit (Muscholl & Vogt, 1958).…”

“…Kroneberg & Schumann (1957a) also demonstrated that recovery was slow and that cutting the splanchnic nerves one week previously only partially protected the glands from depletion. Muscholl & Vogt (1958) found that 14 days were necessary for replacement of the catechol amine content of the rabbit adrenal medulla following depletion by a single intravenous dose of 1.6 mg/kg of reserpine. They also showed that the relative proportions of adrenaline and noradrenaline were normal even in glands still partially depleted at 8 to 9 days.…”

Noradrenaline Content in the Heart and Spleen of the Mouse Under Normal Conditions and After Administration of Some Drugs

“…Even after reserpine, recovery of the cardiac noradrenaline was nearly complete in 48 hr. However, experiments of several authors (Carlsson, Rosengren, Bertler & Nilsson, 1957;Muscholl & Vogt, 1958;Paasonen & Krayer, 1958) have shown in other species that, after depletion by reserpine, it took many days for the concentration of tissue noradrenaline to recover. These results suggested that, in contrast to other species, the stores of noradrenaline in mouse tissues are labile and easily affected by drugs.…”