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The NLRP3 mediates the recruitment of lymphocytes in the cavernosal tissue and erectile function impairment in DOCA/salt mice.
Author(s) -
Fais Rafael Sobrano,
Rodrigues Fernanda Luciano,
Silva Josiane Fernandes,
Tostes Rita C.,
Carneiro Fernando Silva
Publication year - 2018
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.2018.32.1_supplement.718.10
Subject(s) - erectile dysfunction , sodium nitroprusside , medicine , lymphocyte , endocrinology , blood pressure , immune system , nitric oxide , immunology
Erectile dysfunction (ED) is associated with risk factors for the development of cardiovascular diseases such as hypertension. Increased activity of the immune system is closely linked to the development of hypertension and ED. Arterial hypertension is strongly influenced by pro‐inflammatory effects of NLRP3. NLRP3 activity promotes vascular changes, cardiac and renal hypertrophy and increase in blood pressure. In addition, NLRP3 is involved in the recruitment of cells of the immune system. Increasing evidence shows that increased lymphocyte infiltrate is involved in the genesis and/or aggravation of various cardiovascular diseases. Hypothesis NLRP3 increases lymphocyte infiltrate, promotes impairment of corpora cavernosa (CC) reactivity and ED in DOCA/salt hypertensive mice. Objective Evaluate the role of NLRP3 in lymphocyte recruitment in CC, impairment of erectile function and changes in CC reactivity in DOCA/salt mice. Methods (CEUA 213/2016). Male C57BL/6 (WT) and NLRP3 deficient mice (NLRP3 −/− ) were either treated with vehicle or induced to DOCA/salt hypertension. Fluorescence to FAM‐FLICA and histochemistry were performed to analyze respectively the caspase‐1 activity and the number of lymphocytes in CC. The intracavernous pressure (ICP) was measured. Reactivity of CC to acetylcholine (ACh) and sodium nitroprusside (SNP) was performed. Results DOCA/salt hypertension increased the caspase‐1 activity in the CC. In addition, we observed increased lymphocyte infiltrate in the CC (WTsham: 18.5 ± 1.0; WTdoca: 33.5 ± 1.4, n=6), impaired erectile function (decreased ICP in WTdoca in the frequencies of 4, 8, 12 and 16 Hz) and reduced relaxation for ACh (pD 2 WTsham: 7.2 ± 0.08, n=7; WTdoca: 6.5 ± 0.12, n=7) and SNP (pD 2 WTsham: 7.2 ± 0.07, n=6; WTdoca: 6.7 ± 0.06, n=7) in the CC of WT mice. The absence of NLRP3 prevented the increase in the caspase‐1 activity and in the lymphocyte infiltrate (NLRP3 −/− sham: 12.0 ± 1.2; NLRP3 −/− doca: 17.6 ± 1.9, n=5) in the CC. Furthermore, NLRP3 absence normalized the erectile function, the reactivity to ACh (pD 2 NLRP3 −/− sham: 7.0 ± 0,14, n=6; NLRP3 −/− doca: 6.9 ± 0.16, n=7) and to SNP (pD 2 NLRP3 −/− sham: 8.2 ± 0.08, n=6; NLRP3 −/− doca: 8.5 ± 0.07, n=7) in DOCA/salt hypertension. Conclusion NLRP3 mediates the lymphocyte recruitment, impairment in erectile function and CC reactivity, promoted by DOCA/salt hypertension. Support or Funding Information Financial support: FAPESP , CNPq , CAPES, CRID. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .