Chronotropic, inotropic and lusitropic effects of capsaicin on isolated rat atria.
This work includes results on chronotropic, inotropic and lusitropic changes induced by capsaicin on isolated rat atria. As regards spontaneous frequency, it was stimulated from 10(-9) M up to 7 x 10(-7) M of capsaicin. A simultaneous depression in developed force (F) showed a significant correlation with this positive chronotropic effect up to 7 x 10(-8) M of capsaicin, which is the result of the negative staircase phenomenon in the rat heart. The correlation was lost at 2 and 7 x 10(-7) M of capsaicin since in spite of the sustained increase in atrial rate the decrease in F was reversed and then depressed again at 2 and 7 x 10(-6) M of capsaicin without changes in frequency. A concentration of capsaicin that overcome the negative staircase phenomenon, 5 x 10(-7) M, was tested as unique dose resulting in stimulation of the chronotropic, inotropic and lusitropic states of the atria. Percentual differences with respect to control values were maximal after 1-3 minutes for frequency (10 +/- 3%), F (29 +/- 4%), maximal velocity of force development (+F = 50 +/- 12%) (in all cases +F and -F bold indicates +F and -F, respectively), and maximal velocity of relaxation (-F = 64 +/- 13%); a positive lusitropic effect was significant after 8-10 minutes (+F/-F = 17 +/- 7%). Capsaicin did not affect the rat atria in the presence of 10(-6) M of ruthenium red, a blocker of capsaicin activation of sensory nerves, indicating that the stimulatory effects were entirely mediated by the release of neurotransmitters and that this concentration of capsaicin was not deleterous "per se". Capsaicin elicited similar inotropic responses in electrically driven isolated atria (+F = 41 +/- 9%) but the positive lusitropic effect was lost suggesting that capsaicin-induced increases in -F are limited at a frequency higher than the spontaneous frequency (11 +/- 6 vs. 32 +/- 4%, respectively). 10(-6) M of CGRP8-37, an antagonist of CGRP1 receptors, suppress the stimulatory effects of capsaicin on atrial contraction. In summary, atrial rate as compared to atrial contraction is more sensitive to the neurotransmitter released by capsaicin, which results in mechanical effects expressing the negative staircase phenomenon in the rat at low concentrations of capsaicin. The positive chronotropic, inotropic and lusitropic responses elicited by capsaicin are mediated by the release of neurotransmitters from sensory fibbers and no deletereous effects of capsaicin "per se" became evident when the release of neuropeptides was prevented. Atrial contraction was depressed at higher capsaicin concentrations than the one showing stimulatory effects. Stimulation of atrial contractility is mediated by activation of CGRP receptors.
College of Pharmaceuticals of the Provincia of Buenos Aries, Argentina.
A
A
Gomez Alvis
P
P
Quiroga
A
A
Rebolledo
V
V
Milesi
E
E
Mandrile
A
A
Grassi
D000818:Animals; D002211:Capsaicin / Q000032:analysis / Q000494:pharmacology*; D006325:Heart Atria / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000032:analysis* / Q000502:physiology; D012430:Ruthenium Red; D013268:Stimulation, Chemical
D018015:Receptors, Calcitonin Gene-Related Peptide; D012430:Ruthenium Red; D002211:Capsaicin