Summary
In pithed and vagotomized rats the effects of the H3 receptor agonist R-(−)-α-methylhistamine, the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit on basal diastolic blood pressure, basal heart rate and the electrically induced rise in heart rate were examined.
Basal diastolic blood pressure was not altered by low, but increased by high doses of R-(−)-α-methylhistamine; the latter effect was not affected by selective H1, H2 or H3 receptor antagonists and by prazosin, but was attenuated by rauwolscine. Rauwolscine also unmasked a vasodepressor response to R-(−)-α-methylhistamine not affected by the H3 receptor antagonist thioperamide, but counteracted by the H1 receptor antagonist dimetindene or the H2 receptor antagonist ranitidine. The vasodepressor responses to 2-(2-thiazolyl)ethylamine and dimaprit were antagonized by dimetindene and ranitidine, respectively. The vasodepressor response to 2-(2-thiazolyl)ethylamine was not altered by indomethacin, but reduced by an inhibitor of endothelial nitric oxide synthase, Nω-nitro-L-arginine methyl ester (which, by itself, markedly increased blood pressure). Both drug tools did not alter the effect of dimaprit. Basal heart rate was not affected by 2-(2-thiazolyl)ethylamine (examined after administration of propranolol), dimaprit and R-(−)-α-methylhistamine. The electrically induced increase in heart rate (studied in animals which had received rauwolscine) was decreased by R-(−)-α-methylhistamine but not affected by 2-(2-thiazolyl)ethylamine and dimaprit. The effect of R-(−)-α-methylhistamine was abolished by thioperamide. R-(−)-α-methylhistamine did not influence the increase in heart rate produced by isoprenaline.
In conclusion, the pithed rat offers the opportunity to study cardiac presynaptic H3 receptors, endothelial H1 receptors and vascular H2 receptors in the same experimental model. Cardiac presynaptic H1 and H2 receptors as well as postsynaptic H3 receptors in the heart and in the resistance vessels were not found. R-(−)-α-methylhistamine is a weak agonist at α2, H1 and H2 receptors.
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Malinowska, B., Schlicker, E. Identification of endothelial H1, vascular H2 and cardiac presynaptic H3 receptors in the pithed rat. Naunyn-Schmiedeberg's Arch Pharmacol 347, 55–60 (1993). https://doi.org/10.1007/BF00168772
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DOI: https://doi.org/10.1007/BF00168772