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Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea‐pig isolated atria
Author(s) -
Bernoussi Abderrahman,
Rioux Francis
Publication year - 1989
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.1476-5381.1989.tb11854.x
Subject(s) - chronotropic , medicine , endocrinology , histamine , chemistry , bradykinin , inotrope , histaminergic , capsaicin , desensitization (medicine) , receptor , heart rate , blood pressure
1 A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea‐pigs to assess the possible participation of cardiac, capsaicin‐sensitive, substance P (SP)− and calcitonin gene‐related peptide (CGRP)‐containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5‐hydroxytryptamine (5‐HT), histamine, prostaglandin E 2 (PGE 2 ), prostaglandin E 1 (PGE 1 ), prostaglandin F 2α , (PGF 2α ), adrenaline (Ad), glucagon, nicotine and angiotensin II (AII). 2 The positive chronotropic and inotropic effects of Bk, Kd and 5‐HT were markedly reduced in capsaicin‐desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36–81% (chronotropic effect) and 62–86% (inotropic effect); for Kd: 61–78% (chronotropic effect) and 53–77% (inotropic effect); for 5‐HT: 25–66% (chronotropic effect) and 40–64% (inotropic effect)). 3 The positive chronotropic and inotropic effects of histamine, PGE 1 , PGE 2 , PGF 2α , glucagon and AII had similar amplitudes in capsaicin‐desensitized and control atria. 4 The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 × 10 −7 and 7.5 × 10 −6 m Ad were reduced by 41 and 27% respectively, in capsaicin‐desensitized atria compared to control. The chronotropic effects of 1.54 × 10 −5 and 6.17 × 10 −5 m nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin‐desensitized and control atria. 5 These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5‐HT in guinea‐pig atria, unlike those of histamine, PGE 1 , PGE 2 PGF 2α , glucagon and AII, might be the result of stimulation of capsaicin‐sensitive, SP‐ and CGRP‐ containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin‐sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea‐pig atria.