Investigation into different types of post- and presynaptic α-adrenoceptors at cardiovascular sites in rats

Abstract

The effects of 3 α-adrenoceptor agonists of different chemical structure (clonidine, the thiazoloazepine derivative B-HT 920, methoxamine) were studied in pithed rats after i.v. injection. The effect at postsynaptic α-adrenoceptors was determined by the increase in blood pressure and at presynaptic α-adrenoceptors by the inhibition of tachycardia as elicited by electrical stimulation of the spinal sympathetic roots at C 7-Th 1 (pulses, 50 V, 2 msec; 0.2 Hz; 25 sec). Agonist doses which corresponded to a blood pressure increase of 50 mm Hg and to 50% inhibition of the electrically evoked tachycardia respectively (PD 50 and ID 50) were calculated from dose-response curves. The i.v. injection of the α-adrenoceptor antagonists prazosin and yohimbine shifted the dose-response curves of the agonists to the right at both receptor sites. However, the different agonist curves were shifted to different extents by a given dose of the same antagonist. Dose ratios (f) of PD 50 and ID 50 values with various doses of antagonists/without antagonist were calculated and plotted logarithmically against the log of antagonist doses. The antagonist doses which corresponded to f = 10 (D 10) were calculated from the resulting straight lines. The D 10 values revealed that prazosin antagonized methoxamine more effectively than the ‘clonidine-type’ substances clonidine and B-HT 920; yohimbine antagonized the clonidine-type substances more effectively than methoxamine. This pattern was the same at pre- and postsynaptic sites. These results are not compatible with the existence of a single α-adrenoceptor type at both pre- and postsynaptic receptor sites. The results can be explained by the assumption of 2 receptor subtypes pre- as well as postsynaptically (α 1, α 2). The similarities and differences of the pre- and postsynaptic receptor subtypes are discussed.