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B‐HT 958 lowers blood pressure and heart rate in the rat through stimulation of dopamine receptors
Author(s) -
Brown Morris J.,
Harland Deborah
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10825.x
Subject(s) - idazoxan , medicine , endocrinology , heart rate , bradycardia , sulpiride , chemistry , blood pressure , mean arterial pressure , stimulation , antagonist , norepinephrine , dopamine , receptor , prazosin
1 To investigate whether the hypotensive and bradycardiac effects of B‐HT 958 (2‐amino‐6‐(p‐chlorobenzyl)‐4H‐5,6,7,8‐tetrahydrothiazolo‐(5,4‐d) azepine) are due to the stimulation of peripheral prejunctional α 2 ‐adrenoceptors, the selective α 2 ‐adrenoceptor antagonist idazoxan was given either intravenously (i.v.) or intracerebroventricularly (i.c.v.) to anaesthetized rats before the administration of i.v. B‐HT 958. Plasma noradrenaline was used as an approximate index of peripheral sympathetic nervous activity. 2 B‐HT 958 350 μg kg −1 i.v. caused significant falls in blood pressure and heart rate which were maximal 5 min after dosing (− 29.25 ± 3.2 mmHg and − 52 ± 6.8 beats min −1 respectively, mean of all control animals). The hypotension and bradycardia were accompanied by significant falls in plasma noradrenaline concentration of 30–40%. 3 Idazoxan 300 μg kg −1 i.v. caused a marked, but transient tachycardia and a large sustained rise in plasma noradrenaline concentration. Idazoxan 300 μg kg −1 and 1000 μg kg −1 i.v. did not prevent B‐HT 958‐induced falls in mean arterial pressure, heart rate and plasma noradrenaline concentration. Responses to B‐HT 958 were unaffected by idazoxan 20 μg i.c.v. 4 B‐HT 958‐induced falls in mean arterial pressure, heart rate and plasma noradrenaline concentration were significantly attenuated by i.v. administration of the dopamine receptor antagonist, sulpiride 300 μg kg −1 . Sulpiride 10 μg and 50 μg i.c.v. caused inhibition of B‐HT 958 hypotension and bradycardia similar to that of intravenous sulpiride. After i.c.v. sulpiride, B‐HT 958 did not cause a significant fall in plasma noradrenaline concentration. 5 A combination of idazoxan 1000 μg kg −1 i.v. and sulpiride 300 μg kg −1 i.v. did not cause further significant inhibition of B‐HT 958 hypotension and bradycardia compared with sulpiride 300 μg kg −1 i.v. alone. This combination however had a significantly greater effect in inhibiting B‐HT 958 hypotension than had idazoxan 1000 μg kg −1 alone, and almost completely blocked the B‐HT 958‐induced fall in plasma noradrenaline concentration. 6 These results suggest that in the anaesthetized rat the cardiovascular effects of B‐HT 958 are due to stimulation of dopamine receptors, probably located within the central nervous system, and not to stimulation of peripheral prejunctional α 2 ‐adrenoceptors.