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Inhibitory dopamine receptors on sympathetic neurons innervating the cardiovascular system of the pithed rat

Characterization and role in relation to presynaptic α2-adrenoceptors

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Summary

Additional experimental evidence was obtained for an inhibitory function of prejunctional α2-adrenoceptors and/or dopamine receptors located on noradrenergic neurons innervating the heart and resistance vessels of the pithed normotensive rat. Mixed α2-adrenoceptor receptor agonists, differing in selectivity towards either receptor type, i.e. N,N-di-n-propyldopamine (DPDA), 2-N, N-di-n-propylamino-6, 7-dihydroxy-1,2,3,4-tetrahydronaphthalene (DP-6,7-ADTN), B-HT 920 and B-HT 933 (azepexole) were used.

In pithed normotensive rats, DPDA (30 and 100 μg/kg/min) dose-dependently inhibited the electrical stimulation-induced increase in diastolic pressure, but did not significantly affect the stimulation-evoked increase in heart rate. The inhibition exerted by DPDA was blocked by haloperidol and sulpiride (0.3 mg/kg of each), but not by yohimbine (1 mg/kg), indicating the involvement of dopamine receptors. In this respect, sulpiride and haloperidol were found approximately equipotent.

DP-6,7-ADTN (10 and 30 μg/kg/min) impaired both tachycardic and vasoconstrictor responses in a dose-dependent manner. Sulpiride (0.3 mg/kg) only partially restored the DP-6,7-ADTN-depressed stimulation-evoked increase in diastolic pressure, whereas yohimbine (1 mg/kg) alone was without effect. The combination of both antagonists completely prevented the inhibition caused by DP-6,7-ADTN. On the other hand, yohimbine (1 mg/kg), but not sulpiride (0.3 mg/kg), selectively antagonized the DP-6,7-ADTN-induced inhibition of stimulation-evoked tachycardia.

B-HT 920 (1, 3 and 10 μg/kg/min) very effectively reduced the increase in diastolic pressure and heart rate caused by electrical stimulation. Inhibitory dopamine as well as α2-adrenoceptors participated in the vascular effects of B-HT 920, whereas α2-adrenoceptors were only involved in the cardioinhibitory response to this agonist.

B-HT 933 (0.6 and 1 mg/kg/min) dose-dependently reduced the stimulation-evoked increase in arterial pressure through selective stimulation of inhibitory α2-adrenoceptors, dopamine receptors not taking a part.

The results confirm and extend the observations that in addition to α2-adrenoceptors inhibitory dopamine receptors are located on the sympathetic neurons connected with the arterial vasculature of the pithed normotensive rat. The sympathetic nerves innervating the rat heart do not contain inhibitory dopamine receptors; their activity only can be modulated by α2-adrenoceptor stimulation. In the pithed normotensive rat, activation of prejunctionally located α2-adrenoceptors more effectively inhibits the sympathetic activity directed to the heart than that to the resistance vessels.

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Authors and Affiliations

  1. Department of Pharmacy, Division of Pharmacotherapy, University of Amsterdam, Plantage Muidergracht 24, NL-1018 TV, Amsterdam, The Netherlands

    B. Wilffert, G. Smit, A. de Jonge, M. J. M. C. Thoolen, P. B. M. W. M. Timmermans & P. A. van Zwieten

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  1. B. Wilffert
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  2. G. Smit
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  3. A. de Jonge
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  4. M. J. M. C. Thoolen
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  5. P. B. M. W. M. Timmermans
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  6. P. A. van Zwieten
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Wilffert, B., Smit, G., de Jonge, A. et al. Inhibitory dopamine receptors on sympathetic neurons innervating the cardiovascular system of the pithed rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 91–98 (1984). https://doi.org/10.1007/BF00517303

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  • DOI: https://doi.org/10.1007/BF00517303

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