Atrial natriuretic peptide, a regulator of nuclear factor-κB activation in vivo

被引:53
作者
Ladetzki-Baehs, Kathrin
Keller, Melanie
Kiemer, Alexandra K.
Koch, Elke
Zahler, Stefan
Wendel, Albrecht
Vollmar, Angelika M.
机构
[1] Univ Munich, Dept Pharm, Ctr Drug Res, D-81377 Munich, Germany
[2] Univ Saarland, Dept Pharm, D-66041 Saarbrucken, Germany
[3] Univ Konstanz, D-78457 Constance, Germany
关键词
D O I
10.1210/en.2006-0935
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play important roles in the regulation of cardiovascular and renal homeostasis. Along this line, atrial NP (ANP) (international non-proprietary name: carperitide, HANP) is an approved drug for the treatment of acute heart failure. In recent years, evidence has been given that the NP system possesses a far broader biological spectrum than the regulation of blood pressure and volume homeostasis. In fact, a substantial amount of in vitro work indicates that ANP affects important inflammatory processes and signaling pathways. Quite surprisingly, however, no information exists on the in vivo antiinflammatory potential and signaling of ANP. We show here that pretreatment of lipopolysaccharide (Salmonella abortus equi, 2.5 mg/kg)-challenged mice with ANP (5 mu g/kg iv, 15 min) rapidly inhibits nuclear factor-kappa B activation via inhibition of phosphorylation and degradation of the I kappa B-alpha protein. ANP also reduces Akt activation upon lipopolysaccharide injection. In ANP-pretreated mice, the increase of TNF-alpha serum concentration is markedly prevented; most importantly, the survival of these animals improved. These findings demonstrate both in vitro and in vivo an antiinflammatory profile of ANP that deserves to be further investigated in a therapeutic perspective.
引用
收藏
页码:332 / 336
页数:5
相关论文
共 30 条
[1]   Alterations in cell signaling in sepsis [J].
Abraham, E .
CLINICAL INFECTIOUS DISEASES, 2005, 41 :S459-S464
[2]  
Acton RD, 1996, ARCH SURG-CHICAGO, V131, P1216
[3]   Role of NF kappa B in the mortality of sepsis [J].
Bohrer, H ;
Qiu, F ;
Zimmerman, T ;
Zhang, YM ;
Jllmer, T ;
Mannel, D ;
Bottiger, BW ;
Stern, DM ;
Waldherr, R ;
Saeger, HD ;
Ziegler, R ;
Bierhaus, A ;
Martin, E ;
Nawroth, PP .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (05) :972-985
[4]   The immunopathogenesis of sepsis [J].
Cohen, J .
NATURE, 2002, 420 (6917) :885-891
[5]   Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock [J].
Dinarello, CA .
CHEST, 1997, 112 (06) :321S-329S
[6]   NF-κB and rel proteins:: Evolutionarily conserved mediators of immune responses [J].
Ghosh, S ;
May, MJ ;
Kopp, EB .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :225-260
[7]  
GORGEN I, 1992, J IMMUNOL, V149, P918
[8]   N-TERMINAL PROATRIAL NATRIURETIC FACTOR - AN INDEPENDENT PREDICTOR OF LONG-TERM PROGNOSIS AFTER MYOCARDIAL-INFARCTION [J].
HALL, C ;
ROULEAU, JL ;
MOYE, L ;
DECHAMPLAIN, J ;
BICHET, D ;
KLEIN, M ;
SUSSEX, B ;
PACKER, M ;
ROULEAU, J ;
ARNOLD, MO ;
LAMAS, GA ;
SESTIER, F ;
GOTTLIEB, SS ;
WUN, CCC ;
PFEFFER, MA .
CIRCULATION, 1994, 89 (05) :1934-1942
[9]   Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase [J].
Hollenberg, SM ;
Broussard, M ;
Osman, J ;
Parrillo, JE .
CIRCULATION RESEARCH, 2000, 86 (07) :774-778
[10]   Inhibition of aldosterone and endothelin-1 by carperitide was attenuated with more than 1 week of infusion in patients with congestive heart failure [J].
Ishikawa, C ;
Tsutamoto, T ;
Wada, A ;
Fujii, M ;
Ohno, K ;
Sakai, H ;
Yamamoto, T ;
Horie, M .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2005, 46 (04) :513-518