The Contribution of alpha2-Adrenoceptors to Sympathetic Neuroeffector Transmission in the Rabbit Isolated Saphenous and Plantaris Veins

Daly, Craig James (1993) The Contribution of alpha2-Adrenoceptors to Sympathetic Neuroeffector Transmission in the Rabbit Isolated Saphenous and Plantaris Veins. MSc(R) thesis, University of Glasgow.

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Abstract

1 The aim of the study was to establish i) the presence or absence of postjunctional alpha2-adrenoceptors on the rabbit isolated saphenous and plantaris veins, ii) the contribution of these receptors (if any) to sympathetic neuroeffector transmission in both vessels, iii) the conditions which may influence their contribution to the neuroeffector response. 2 Based on the rank order of alpha-adrenoceptor subtype specific agonist potency (UK 14304 > NA >> phenylephrine) and antagonist potency (rauwolscine = prazosin > corynanthine), the saphenous vein was considered to possess a mixed population of postjunctional alpha1- and alpha2-adrenoceptors. A possible interaction between these receptors is discussed. 3 Based on the rank order of alpha-adrenoceptor subtype specific agonist potency (UK 14304 > NA >> phenylephrine) and antagonist potency (rauwolscine > corynanthine >> prazosin), the plantaris vein was considered to possess a more homogeneous population of functional postjunctional alpha2-adrenoceptors than the saphenous vein. 4 The effects of relatively selective alpha-adrenoceptor antagonists, on the response to electrical field stimulation (EFS), in the saphenous vein suggested that alpha1-adrenoceptors play a major role in the neurovascular response. 5 Responses to EFS in the saphenous vein were unaffected by either propranolol or corticosterone. Cocaine, however, was found to potentiate the height and, more significantly, to prolong the time course of the response to EFS in the saphenous vein. 6 The effects of selective a-antagonists, in the presence of cocaine, indicated a small contribution from postjunctional alpha2-adrenoceptors to the response to EFS in the saphenous vein. 7 The apparent lack of effect of rauwolscine and the inhibitory effect of prazosin on responses to EFS in the plantaris vein indicated that, in the absence of cocaine, alpha1- adrenoceptors play a major role in neuroeffector transmission in this vessel. 8 In the presence of cocaine, rauwolscine caused a significant inhibition of responses to EFS in the plantaris vein. The effect of prazosin however was unaffected. This indicates that, in the presence of cocaine, postjunctional alpha2-adrenoceptors play a significant role in neuroeffector transmission. 9 The non-adrenergic component of the response to EFS in the plantaris vein was found to be highly sensitive to inhibition by alpha-beta,methyleneATP. This suggests that NA & ATP are co-transmitters in the sympathetic nerves of the plantaris vein. 10 As mentioned above (point 5), cocaine increased the duration of the response to EFS in the saphenous vein. This resulted from the emergence of a secondary phase of the response to EFS above 8Hz which was highly sensitive to inhibition by the alpha2-adrenoceptor antagonists rauwolscine and CH 38083. The first phase was sensitive to alpha1-adrenoceptor antagonists. Thus in the presence of cocaine, alpha2-adrenoceptors provide a major contribution to the neurovascular response above 8Hz. 11 Lowering the PO2 in the saphenous vein caused the appearance of a secondary phase of the response to EFS. In low O2 prazosin was found to be slightly less effective but the effect of rauwolscine was no greater. This indicated that merely lowering P02 was not sufficient to recruit a significant population of postjunctional alpha2-adrenoceptors for the response to neuroeffector transmission. 12 In the absence of cocaine and in the presence of selective alpha-adrenoceptor antagonists, angiotensin II (All) did not potentiate responses to EFS in the saphenous vein. In the presence of cocaine and prazosin however All caused a significant potentiation of response at 16Hz and above. Thus All has a facilitatory effect on postjunctional alpha2-adrenoceptors when neuronal uptake is blocked. 13 All caused potentiation of responses to EFS in the plantaris vein only in the presence of prazosin and regardless of the presence of cocaine. Therefore, AH can be shown to have a selective potentiating effect on postjunctional alpha2-adrenoceptors which are involved in the response to EFS in both the saphenous and plantaris veins. 14 The sensitivity to selective and non-selective alpha-adrenoceptor agonists in the saphenous vein was unaffected by removal of the endothelium. The maximum response to the alpha1-adrenoceptor agonists was however increased. This suggests that endogenous nitric oxide (NO) liberated from the endothelium has an inhibitory effect on responses mediated by postjunctional alpha1- but not alpha2-adrenoceptors. 15 The effect of L-NAME (an inhibitor of NO synthetase) was assessed on the biphasic response to EFS and the response to exogenous NA in the saphenous vein. L-NAME caused a marked potentiation of the response to EFS. However, no selective effect on either phase was found. Endogenous NO had more of an effect on those receptors involved in the response to EFS than those involved in the response to exogenously applied agonists. 16 In conclusion, functional alpha2-adrenoceptors are present on both the saphenous and plantaris veins. The addition of cocaine, to block neuronal uptake and thus increase the concentration or duration of NA in the neuroeffector junction, can enhance the contribution of alpha2-adrenoceptors to the response to neuroeffector transmission. All can also enhance the contribution of alpha2-adrenoceptors to the neurovascular response. It is not certain whether changes in PO2 or basal levels of NO can selectively augment alpha2- adrenoceptor function although these factors can modulate the alpha-adrenoceptor mediated response to neuroeffector transmission in the saphenous vein.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: J C McGrath
Keywords: Neurosciences, Physiology
Date of Award: 1993
Depositing User: Enlighten Team
Unique ID: glathesis:1993-75616
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 19:17
Last Modified: 19 Nov 2019 19:17
URI: http://theses.gla.ac.uk/id/eprint/75616

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