Degeneration of sympathetic nerves <i>in vitro</i> and development of smooth muscle supersensitivity to noradrenaline

Geffen, L. B.; Hughes, Chris

doi:10.1113/jphysiol.1972.sp009739

Cited by 23 publications

(4 citation statements)

References 18 publications

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“…Furness (1 97 1) attributed these spontaneous contractions (which were shown to be blocked by phenoxybenzamine) to degeneration-induced release of noradrenaline. This phenomenon is similar to, but occurs earlier than, the degeneration contraction which occurs in vivo following surgical denervation of periorbital smooth muscle of the rat (Lundberg, 1969), the ear blood vessels and iris of the rabbit (Emmelin & Ohlin, 1969;Barany & Triester, 1970), the nictitating membrane of the cat (Langer, 1966) and the expansor-secundariorum muscle of the chicken (Geffen & Hughes, 1972). In the present study, the spontaneous contractions and the enhancement of the response to KCl above control values, in epididymal segments 2 days after vasectomy, were abolished following incubation of the tissues with guanethidine.…”

Section: Discussionmentioning

confidence: 56%

Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy

Pennefather

1987

Journal of Autonomic Pharmacology

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1 The effects of some sympathomimetic amines and of carbachol and potassium chloride upon the contractility of epididymal halves of the rat vas deferens have been examined in vitro at several times following vasectomy by medial transection of the vas deferens in vivo. The inhibitory effects of noradrenaline and the excitatory effects of potassium chloride upon prostatic halves of transected tissues were also studied. 2 Partially denervated epididymal segments, taken 2 days after surgery, were spontaneously active, and responses to KCl (80 mmol/l) and maximum responses to phenylephrine were enhanced. These effects were not observed with preparations taken at later times. Spontaneous activity and enhancement of responses to KCl were abolished by guanethidine (0.1 mumol/l). 3 Supersensitivity to noradrenaline was observed in fully denervated epididymal halves of vasa deferentia taken 7-183 days after transection. The supersensitivity consisted of a leftward shift in the log concentration-response curves for noradrenaline constructed upon operated, relative to those obtained upon unoperated preparations. Supersensitivity to phenylephrine but not to methoxamine or to carbachol was also evident. 4 The magnitude of the leftward shift in the log concentration-response curve for noradrenaline in operated epididymal segments approached that produced, in unoperated segments, by nisoxetine (0.1 mumol/l). This inhibitor of neuronal uptake did not enhance the potency of noradrenaline in operated segments. 5 Prazosin (50 nmol/l) antagonized the effect of phenylephrine upon both operated and unoperated epididymal segments. The antagonism was significantly greater upon operated segments than upon unoperated segments 4 and 28 days after surgery. 6 In prostatic segments, noradrenaline produced inhibition of field stimulation-induced twitches. Its potency was similar in both operated and unoperated preparations, and nisoxetine (0.1 mumol/l) potentiated its effects to a similar extent (approximately 70-fold) in control and operated tissues. Responses to KCl in this half of the vas deferens were essentially unaffected by vasectomy. 7 Taken together, these findings indicate that post-ganglionic denervation of the epididymal half of the rat vas deferens by medial transection (vasectomy) leads to a slowly developing and prolonged supersensitivity to noradrenaline which is primarily due to the loss of the neuronal uptake facility. Persistent adaptive changes in the effector cells are apparently minimal after this means of denervation.

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Section: Discussionmentioning

confidence: 56%

Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy

Pennefather

1987

Journal of Autonomic Pharmacology

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“…Since it has been shown that surgical denervation of the ESM for 3 days causes degeneration of its noradrenergic nerve terminals without affecting the postsynaptic receptors (Geffen & Hughes, 1972) this provides a means of assessing the number of presynaptic receptors in the ESM. In the present study it was observed that there was a reduction in [3-3H]-QNB binding of 0.6 fmol/mg protein when ESMs from either 23 or 57 day old chicks were denervated 3 days previously.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Noradrenergic Denervation on Muscarinic Receptors of Smooth Muscle

Bennett

Lot

Strange

1982

British J Pharmacology

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Changes in the response to acetylcholine of expansor secundariorum muscles from chicks have been analysed by pharmacological techniques and by [3‐3H]‐quinuclidinyl benzilate ([3‐3H]‐QNB) binding to quantify the muscarinic receptor population. The expansor secundariorum muscle responded to acetylcholine up to the age of 30 days; the response declined thereafter. This developmental decrease in response to acetylcholine was prevented by surgical denervation. In chicks aged less than 25 days, denervation did not affect the sensitivity of the expansor muscle to acetylcholine. In older chicks (above 40 days) denervation gradually restored the sensitivity of the expansor muscle to acetylcholine. Responses of the expansor muscle were always abolished by atropine (1 μm) indicating they were mediated by muscarinic receptors. Binding studies with [3‐3H]‐QNB showed that changes in response of expansor muscles to acetylcholine were primarily due to changes in the muscarinic receptor population. It is suggested that the noradrenergic innervation of the expansor muscle influences the number of muscarinic receptors expressed in the tissue.

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“…It might be argued, for example, that both the chemical and electrolytic lesions of the ventrolateral medulla evoked degeneration release of the transmitter (Geffen and Hughes, 1972) in a pressor system, thus causing the transient increase in pressure which was noted in Figures 4-7. On the other hand, the increase in pressure is associated with vasoconstriction (Fig.…”

Section: Vasomotor Changesmentioning

confidence: 99%

Hypertension, bradycardia, and pulmonary edema in the conscious rabbit after brainstem lesions coinciding with the A1 group of catecholamine neurons.

Blessing¹,

West²,

Chalmers³

1981

Circulation Research

120

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We studied the effects of lesions in the ventrolateral medulla, in a region coinciding with the cell bodies of the Al group of catecholamine neurons. After bilateral electrolytic lesions at three contiguous rostrocaudal levels (obex and at 1 and 2 mm caudal to the obex), mean arterial pressure increased by 40 mm Hg in the conscious rabbit. This rise in pressure was associated with increased resistance in the distal aortic vascular bed and with profound bradycardia. Many lesioned animals developed respiratory distress in the first few postoperative hours and died with hemorrhagic pulmonary edema. In surviving rabbits, the distal aortic resistance remained raised throughout the 2-week observation period, but the blood pressure and heart rate returned to preoperative levels within 2 hours and then remained normal. Bilateral electrolytic lesions restricted to the level of the obex or to a level 1 mm caudal to tbe obex also caused transient hypertension and bradycardia, but most of the animals survived this more restricted damage and did not develop pulmonary edema. Micro-injections of kainic acid, a neurotoiin that specifically damages cell bodies, also caused transient hypertension and bradycardia, and after larger doses the rabbits died with acute pulmonary edema. Injections of 6hydroxydopamine caused similar changes in pressure and heart rate, but doses necessary to destroy the Al cells caused nonspecific histological damage of an extent similar to that produced by electrolytic lesions. Sham-lesioned animals and those with control lesions in adjacent sites did not develop these cardiovascular changes. These experiments suggest that the persistent increase in peripheral resistance after lesions of the ventrolateral medulla results from destruction of neurons that normally act to inhibit sympathetic vasoconstrictor tone. It is our hypothesis that the increase in vascular resistance after the lesions results from destruction of the Al catecholamine cells within this ventrolateral region. CircRea 49; [949][950][951][952][953][954][955][956][957][958] 1981

show abstract

Degeneration of sympathetic nerves in vitro and development of smooth muscle supersensitivity to noradrenaline

Cited by 23 publications

References 18 publications

Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy

Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy

The Effects of Noradrenergic Denervation on Muscarinic Receptors of Smooth Muscle

Hypertension, bradycardia, and pulmonary edema in the conscious rabbit after brainstem lesions coinciding with the A1 group of catecholamine neurons.

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