Further sub-classification of alpha-adrenoceptors in the cardiovascular system, vas deferens and anococcygeus of the rat [proceedings].
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Biomedical subjects
Publications and source records attributed to J R Docherty.
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The pattern of innervation on individual iliotibialis muscle fibres from axolotl (Ambystoma mexicanum) has been investigated histologically and electrophysiologically. These polyneural fibres were found to be innervated on average at five end plate sites. The sites were distributed irregularly along each fibre. Average end plate length was found to be approximately 70 micrometer. Most end plates were separated by less than 1000 micrometer; 26% by less than 150 micrometer; the average separation was 516 micrometer. Advantage was taken of the dual innervation of the muscle to investigate the separation between synaptic terminals from different axons. Some individual fibres were found to be innervated by axons from two different spinal nerves. End plate sites on dually innervated fibres were located by ACh iontophoresis. 30% of such sites were found to be innervated by more than one axon terminal. The average separation of such sites was found to be 9 micrometer. Four different axons were found to innervate some individual muscle fibres. It is suggested that the unusual ability of axolotl muscle fibres to accept synaptic terminals from different axons at closely adjacent sites may be a major factor underlying selective reinnervation in this animal.
1. The effects of pancuronium bromide on the cardiovascular system of the pithed rat were examined. Pancuronium had two effects, a short-lasting cardiovascular stimulation following injection and a longer-lasting potentiation of responses to sympathetic nerve stimulation. 2 The initial effect of pancuronium was compared with that of tyramine. The cardioaccelerator but not the pressor responses to both pancuronium and tyramine were significantly reduced following sympathectomy with 6-hydroxydopamine (6-OHDA). 3 The action of pancuronium in potentiating sympathetic nerve responses was compared with that of known blockers of the neuronal uptake of noradrenaline (NA). Pancuronium (1 mg/kg) and cocaine (0.5 mg/kg) potentiated cardioaccelerator and pressor responses to sympathetic stimulation. These effects of pancuronium could be obtained following adrenalectomy and during neuromuscular blockade with gallamine. Pancuronium and uptake blockers potentiated the cardioaccelerator response to NA, reduced the response to tyramine, but did not affect the response to isoprenaline. Pancuronium and uptake blockers potentiated the pressor response to NA, but did not affect the response to tyramine or clonidine. 4 Following sympathectomy with 6-OHDA, pancuronium failed to potentiate cardioaccelerator and pressor responses to NA. 5 These results are discussed in relation to two main cardiovascular effects of pancuronium; an indirect sympathomimetic action and blockade of the neuronal uptake of NA.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Pre- and postsynaptic alpha-adrenoceptors in autoperfused rabbit hindlimbs were examined employing the yohimbine diastereomers rauwolscine and corynanthine, as well as other drugs with varying selectivities for alpha 1-and alpha 2-adrenoceptors. Vasoconstrictor responses were elicited by sympathetic nerve stimulation and by intraarterial injection of agonists. The alpha 2-selective antagonist rauwolscine (10(-7) and 10(-6) M) reduced responses to injected noradrenaline (mixed alpha 1- and alpha 2-agonist) but not to injected phenylephrine (alpha 1-selective agonist); rauwolscine (10(-6) M) actually enhanced nerve-mediated responses. Corynanthine (alpha 1-selective antagonist) was about equipotent against agonist- and nerve-mediated responses. In another series of experiments, rauwolscine (10(-6) M) strongly antagonized the response to xylazine (alpha 2-selective agonist), antagonized the responses to alpha-methylnoradrenaline and noradrenaline (mixed agonists) less strongly, and did not affect the response to phenylephrine, Conversely, prazosin (alpha 1-selective antagonist, 10(-8) M) strongly antagonized phenylephrine, antagonized noradrenaline and alpha-methylnoradrenaline less strongly, and did not antagonize xylazine. Potentiation of neuroeffector responses by rauwolscine demonstrates the operation of an endogenous autoinhibition of noradrenaline release mediated by presynaptic alpha 2-adrenoceptors. However, in comparison with previous in vitro results on rabbit pulmonary artery, the potentiation was small due to the presence of postsynaptic alpha 2-adrenoceptors.
Postsynaptic alpha-adrenoceptor subtypes were investigated in vitro, employing rabbit aorta, pulmonary artery, and portal vein, and rat anococcygeus. Phenylephrine (alpha 1-selective), alpha-methylnoradrenaline (mixed agonist), and xylazine (alpha 2-selective) were used as agonists, and prazosin (alpha 1-selective) and rauwolscine (alpha 2-selective) as antagonists. In all tissues, agonist concentration-response curves were monophasic and their shape was unaltered by either antagonist. In rabbit blood vessels, prazosin was as potent against alpha-methylnoradrenaline as against phenylephrine and was 1,000 times more potent than rauwolscine; xylazine was a partial agonist of low potency. Hence, the postsynaptic receptors of these tissues are alpha 1. In the rat anococcygeus, there was some evidence for an alpha 2-receptor: xylazine was a full and potent agonist, rauwolscine was more potent against xylazine than against alpha-methylnoradrenaline or phenylephrine, and in experiments protecting against irreversible blockade by phenoxybenzamine, xylazine afforded significantly greater protection to alpha-methylnoradrenaline than to phenylephrine. However, prazosin was more potent than rauwolscine against xylazine and was equipotent against all agonists. Hence, although the smooth muscle cells of the rat anococcygeus may contain alpha 2-adrenoceptors, the predominant population is alpha 1.
We examined the blood pressure-lowering effects of the alpha 2-adrenoceptor antagonist rauwolscine in anaesthetised spontaneously hypertensive rats (SHR). In the absence of prior drug, rauwolscine (1-10 mg kg-1) produced dose-dependent falls in diastolic blood pressure (DBP). In the presence of prazosin (1 mg kg-1) to eliminate alpha 1-adrenoceptor-mediated responses, rauwolscine (0.1-1 mg kg-1) lowered DBP in unoperated and sham-operated animals but not in adrenal demedullated animals. Hence, we were able to demonstrate that alpha 2-adrenoceptors are involved in the control of blood pressure in intact anaesthetised SHR but not following adrenal demedullation, suggesting that circulating catecholamines are responsible for these alpha 2-adrenoceptor-mediated pressor effects.
We have looked at the role played by alpha 1 and alpha 2 adrenoceptors in the control of blood pressure in the anaesthetised spontaneously hypertensive rat (SHR) by examining the blood-pressure-lowering effects of the alpha 1-adrenoceptor antagonist prazosin and the alpha 2-adrenoceptor antagonist rauwolscine in 5 groups of animals: unoperated, adrenal demedullated, shamoperated, sympathectomised with 6-hydroxydopamine, and vehicle treated. Prazosin (1 mg/kg) produced significant falls in diastolic blood pressure (DBP) in all groups of rat but the fall was significantly less in sympathectomised animals. In the presence of prazosin (1 mg/kg), rauwolscine (0.1-1 mg/kg) lowered DBP in all groups of rat except the adrenal demedullated animals. In the absence of prazosin, rauwolscine (0.1 mg/kg) produced a significant fall in DBP only in sympathectomised animals. These results demonstrate that alpha 2 adrenoceptors are involved in blood pressure control in the intact or sympathectomised SHR but not following adrenal demedullation, suggesting that circulating catecholamines rather than neurally released noradrenaline (NA) are responsible for these alpha 2-adrenoceptor-mediated pressor effects. In contrast, only alpha 1-adrenoceptor-mediated pressor responses are reduced by sympathectomy, suggesting that neurally released NA acts mainly on alpha 1-adrenoceptors.
We examined baroreflex function and cardiac responsiveness in young (3-7 months) and old (21-24 months) Sprague-Dawley rats. Nitroprusside was more effective in lowering diastolic blood pressure (DBP) in old than in young conscious animals, but there was no such difference in anaesthetised animals. In conscious animals, the slope of the regression line for the fall in DBP produced by nitroprusside against the resultant tachycardia was significantly steeper for young animals, so that a given fall in DBP produced a greater rise in heart rate in young animals. In anaesthetised or pithed animals, the tachycardia produced by isoprenaline, noradrenaline, and single-pulse electrical stimulation did not differ between young and old animals. Hence, we have evidence that baroreflex sensitivity is reduced in aged rats, but that this is not due to a decreased responsiveness of the heart.