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Central administration of 5‐HT activates 5‐HT 1A receptors to cause sympathoexcitation and 5‐HT 2 /5‐HT 1C receptors to release vasopressin in anaesthetized rats
Author(s) -
Anderson Ian K.,
Martin Graeme R.,
Ramage Andrew G.
Publication year - 1992
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.1476-5381.1992.tb13401.x
Subject(s) - endocrinology , medicine , vasopressin , chemistry , bradycardia , antagonist , vasopressin receptor , receptor , receptor antagonist , heart rate , blood pressure
1 The effects of intracerebroventricular injections to the right lateral ventricle (i.c.v.) of 5‐hydroxytryptamine (5‐HT, 40 and 120 nmol kg −1 ), N,N‐di‐n‐propyl‐5‐carboxamidotryptamine (DP‐5‐CT; 3 nmol kg −1 ), 5‐carboxamidotryptamine (5‐CT; 3 nmol kg −1 ), 8‐hydroxy‐2‐(di‐N‐propylamino) tetralin (8‐OH‐DPAT; 3, 40 and 120 nmol kg −1 ) and 1‐(2,5‐di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI; 40 and 120 nmol kg −1 ) on renal sym pathetic nerve activity, blood pressure, heart rate and phrenic nerve activity were investigated in normotensive rats anaesthetized with α‐chloralose. 2 5‐HT caused a long lasting pressor response which was associated with an initial bradycardia and renal sympathoinhibition followed by a tachycardia and renal sympathoexcitation. Pretreatment with the 5‐HT 2 /5‐HT 1C receptor antagonists, cinanserin (300 nmol kg −1 , i.c.v.) or LY 53857 (300 nmol kg −1 , i.c.v.) reversed the initial bradycardia and sympathoinhibition to tachycardia and sympathoexcitation. Combined pretreatment with LY 53857 (300 nmol kg −1 , i.c.v.) and the 5‐HT 1A antagonist, spiroxatrine (300 nmol kg −1 , i.c.v.), blocked the effects of 5‐HT on all the above variables. 3 Pretreatment with the vasopressin V 1 ‐receptor antagonist, β‐mercapto‐β,β‐cyclopentamethylenepropionyl 1 , O‐Me‐Tyr 2 , Arg 8 ‐vasopressin [(d(CH 2 ) 5 Tyr(Me)AVP, 10 μg kg −1 , i.v.] did not affect the magnitude but reduced the duration of the pressor response produced by i.c.v. 5‐HT and reversed the initial bradycardia and renal sympathoinhibition to tachycardia and sympathoexcitation. 4 1‐(2,5‐Di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) caused a pressor effect which was associated with a bradycardia and sympathoinhibition. These effects were blocked by pretreatment with BW501C67 (0.1 mg kg −1 , i.v.), a peripherally acting 5‐HT 2 /5‐HT 1C receptor antagonist. However, BW501C67 (0.1 mg kg −1 , i.v.) failed to block the effects of i.c.v. 5‐HT. 5 DP‐5‐CT, 5‐CT and 8‐OH‐DPAT (3 nmol kg −1 , i.c.v.) caused sympathoexcitation, tachycardia and a rise in blood pressure. Pretreatment with methiothepin (1 mg kg −1 , i.v.) or spiroxatrine (300 nmol kg −1 , i.c.v.) attenuated the response to i.c.v. DP‐5‐CT. 6 It is concluded that i.c.v. administration of 5‐HT activates 5‐HT 1A receptors to cause sympathoexcitation and 5‐HT 2 or 5‐HT 1C receptors to cause the release of vasopressin.