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Influence of respiratory acidosis or alkalosis on pressor responses mediated byα 1- andα 2-adrenoceptors in pithed normotensive rats

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Summary

The effect of respiratory acidosis and alkalosis on the vasoconstriction toα 1- andα 2-adrenoceptor stimulation was studied in pithed normotensive rats. The selectiveα 1-adrenoceptor agonists (-)amidephrine, cirazoline, (±)erythro methoxamine (-)phenylephrine, Sgd 101/75 and St 587 were used, as well as the selectiveα 2-adrenoceptor agonists B-HT 920, B-HT 933, DP-6,7-ADTN, M-7 and UK 14,304. The non-selectiveα-adrenoceptor agonists xylazine, noradrenaline and adrenaline were included as well. The latter two were also studied under selective doses of the antagonists rauwolscine and prazosin, thus yielding the respectiveα 1- andα 2-adrenoceptor components of the vasoconstriction to these agonists. The effect of acid-base balance disturbances on presynaptically released noradrenaline elicited by electrical stimulation of preganglionic nerves was studied as well. Dose response curves for the agonists were generated under various conditions of ventilation, yielding either alkalotic, normal or acidotic values of arterial blood pH. Pressor responses to all agonists were maximally affected by changes in acid-base status at the low doses of the agonists. Acidosis was found to inhibit increases in diastolic pressure mediated by theα 1- as well as theα 2-adrenoceptor agonists studied, although not to the same extent. Alkalosis exerted either an obvious potentiation or did not significantly influenceα 1-adrenoceptor mediated pressor responses. On the basis of acid-base sensitivity the following groups of agonists were distinguised: (1) Cirazoline, phenylephrine, methoxyamine, electrically released noradrenaline from presynaptic sites, of which pressor responses are obviously potentiated and attenuated by alkalosis and acidosis, respectively. (2) Sgd 101/75, St 587, noradrenaline-α 1, amidephrine and adrenaline-α 1, eliciting pressor responses which are strongly acid-sensitive and base-insensitive. (3) B-HT 920, B-HT 933, DP-6, 7-ADTN (lower doses), of which vasoconstriction is markedly inhibited by both acidosis and alkalosis. (4) Noradrenaline-α 2, UK 14,304, M-7 (lower doses), adrenaline-α 2 and high doses of the agonists of the former group. Pressor responses of these agonists were found to be not or slightly base-sensitive, but profoundly acid-sensitive. Xylazine does not fit into this classification. The present data are not in accordance with purported subdivisions ofα-adrenoceptor agonists by others. It is therefore concluded that the differential effect of acid-base status onα-adrenoceptor mediated vasoconstriction in pithed rats is an exponent of the differential way of interaction of the agonists with the adrenoceptors involved.

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Author notes

  1. A. de Jonge

    Present address: Dr. Karl Thomae GmbH, Birkendorffer Straße 65, Postfach 720, D-7959, Biberach 1, FRG

Authors and Affiliations

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

    C. Korstanje, M -J. Mathy, K. van Charldorp, A. de Jonge & P. A. van Zwieten

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  1. C. Korstanje
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  2. M -J. Mathy
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  3. K. van Charldorp
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  4. A. de Jonge
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  5. P. A. van Zwieten
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Additional information

Preliminary data were communicated at the Joint Meeting of the French and German Pharmacological and Toxicological Societies, Feiburg i. Br., September 19–22, 1983 (De Jonge et al. 1983)

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Korstanje, C., Mathy, M.J., van Charldorp, K. et al. Influence of respiratory acidosis or alkalosis on pressor responses mediated byα 1- andα 2-adrenoceptors in pithed normotensive rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 330, 187–192 (1985). https://doi.org/10.1007/BF00572433

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  • DOI: https://doi.org/10.1007/BF00572433

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