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Capsazepine decrease the pressor response to stimuli other than transient receptor potential vanilloid‐1 agonists
Author(s) -
Ducrocq Guillaume P,
Estrada Juan A,
Kim Joyce S,
Kaufman Marc P
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb492
Subject(s) - capsazepine , trpv1 , chemistry , capsaicin , bradykinin , reflex , medicine , stimulation , endocrinology , transient receptor potential channel , agonist , pharmacology , receptor , biochemistry
Capsaicin‐induced stimulation of Transient Receptor Potential Vanilloid‐1 (TRPV1) receptors on thin fiber muscle afferents reflexively increases arterial blood pressure in multiple species of mammals. In rats, blocking these receptors with capsazepine reduced the pressor response to contraction of the hindlimb muscles, a finding which suggests that TRPV1 receptors mediate the exercise pressor reflex. Capsazepine, however, has been shown in vitro to block voltage gated calcium channels, raising the possibility that it might have reduced the exercise pressor reflex by another mechanism. To test that alternative, we examined the effect of capsazepine on the pressor responses to intra‐arterial injection of bradykinin and diprotonated phosphate, metabolic by‐products of contraction believed to play a role in the elicitation of the exercise pressor reflex. In decerebrated Sprague‐Dawley rats, we injected bradykinin (1.5 μg/kg, 0.1 mL; n = 9) or diprotonated phosphate (86 mM, pH = 6.0, 0.2 mL; n = 3) into the arterial supply of the hindlimb before and after injecting capsazepine (100 μg/mL, 0.1 mL). We challenged the effectiveness of capsazepine to inhibit TRPV1 receptors by injecting the specific TRPV1 agonist, capsaicin (0.5 μg/kg, 0.1 mL). Capsazepine decreased the pressor response to capsaicin (50 ± 11 mmHg vs .32 ± 14 mmHg [mean ± SD]; p = 0.06, d = 1.03) and to bradykinin (25 ± 8 mmHg vs .13 ± 12 mmHg; p = 0.03, d = 0.85). The effect of capsazepine on the pressor response to diprotonated phosphate was unclear due to a small sample size (44 ± 25 mmHg vs. 31 ± 29 mmHg). Intra‐arterial injection of the vehicle for capsazepine had no effect on the pressor responses to bradykinin, diprotonated phosphate and capsaicin. Our data suggest that capsazepine is not a selective antagonist to TRPV1 receptors and should not be used to test the hypothesis that TRPV1 receptors on thin fiber afferents play a role in evoking the exercise pressor reflex. Support or Funding Information Supported by NIH P01 HL 134609. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .