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Facilitation by procaterol, a β‐adrenoceptor agonist, of noradrenaline release in the pithed rat independently of angiotensin II formation
Author(s) -
Kotsonis P.,
Majewski H.
Publication year - 1994
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.1476-5381.1994.tb17061.x
Subject(s) - methoxamine , medicine , endocrinology , angiotensin ii , stimulation , chemistry , sympathetic nervous system , blood pressure , agonist , receptor
1 The effects of the β 2 ‐adrenoceptor agonist, procaterol, on sympathetic neuroeffector transmission were studied in the pithed adrenal demedullated rat to determine if generation of angiotensin II was involved in its effect. Pressor responses were elicited by either electrical stimulation (20 V, 2 Hz) of the entire spinal sympathetic outflow or methoxamine (0.1 mg kg −1 , i.v.). 2 Sodium nitroprusside (3 and 5 μg −1 min −1 , i.v.) produced hypotension and the pressor responses to both sympathetic nerve stimulation and methoxamine were reduced. This indicates that decreasing blood pressure in pithed rats reduces pressor responses. Procaterol (10 and 30ng kg −1 min −1 , i.v.) also produced hypotension but did not alter pressor responses to sympathetic nerve stimulation. Nevertheless, procaterol (10 and 30 ng kg −1 min −1 , i.v.) did reduce pressor responses to methoxamine. Together these results suggest that procaterol may have enhanced sympathetic neurotransmitter release. This was confirmed in another series of experiments where procaterol (30ngkg −1 min −1 , i.v.) increased plasma noradrenaline levels during sympathetic nerve stimulation. 3 Captopril (5 mg kg −1 , i.v.) produced hypotension and as expected reduced pressor responses to sympathetic nerve stimulation. When the hypotensive effect of captopril was abolished by concomitant vasopressin infusion (1.5‐4.5 i mu kg −1 min −1 , i.v.), pressor responses to sympathetic nerve stimulation were restored to pre‐captopril levels. In this situation procaterol (10 and 30 ng kg −1 min −1 , i.v.) reduced basal blood pressure and did not alter pressor responses to sympathetic nerve stimulation whereas the pressor responses were reduced by an equihypotensive infusion of sodium nitroprusside (3 and 5 μg kg −1 min −1 , i.v.). The lack of reduction of pressor responses after procaterol in the presence of captopril is indirect evidence that procaterol may have enhanced noradrenaline release independently of angiotensin II. 4 In another series of experiments, plasma noradrenaline levels elicited by sympathetic nerve stimulation were not altered by captopril (5 mg kg −1 , i.v.). In the presence of captopril (5 mg kg −1 , i.v.), procaterol (30 ng kg −1 min −1 , i.v.) no longer enhanced plasma noradrenaline levels during sympathetic nerve stimulation. However, since the dose of captopril is well above that required to block angiotensin converting enzyme (ACE) the effect may be non‐specific. Therefore, the selective AT 1 receptor antagonist, losartan (10 mg kg −1 , i.v.), was also used. Losartan (10 mg kg −1 , i.v.) did not alter plasma noradrenaline levels during sympathetic nerve stimulation, and in the presence of losartan procaterol (30 ng kg −1 min −1 , i.v.) enhanced plasma noradrenaline levels during sympathetic nerve stimulation. This result further suggests that β‐adrenoceptor facilitation of noradrenaline release from sympathetic nerves in the pithed rat occurs by a mechanism independent of angiotensin II generation.