Abstract 649: Heme-oxygenase-1 Induction Improves Type-1 Cardiorenal Syndrome Only In Mice With Impaired AngII-induced Lymphocyte Activation (SCID Mice)

Abstract

Rational: The absence of lymphocyte activity protects SCID mice from AngII-induced hypertension facilitating blood pressure-induced sodium excretion, possibly via the stimulation of eNOS- and COX-2-dependent pathways. Type-1 cardiorenal syndrome (CRS-1), characterized by acute kidney dysfunction secondary to deterioration in cardiac function, is caused by renal arteriolar vasoconstriction, mediated by the activation of renin-angiotensin and sympathetic nervous systems (RAAS, SNS). Heme Oxygenase-1 (HO-1) induction improves renal function, but not renal vasoconstriction, in AngII-induced hypertension, and causes the desensitization of vascular smooth muscle to phenylephrine.

Objectives: We evaluated whether AngII resistant SCID mice develop CRS-1 as occurs in control mice, and the differential effects of HO1 induction on renal hemodynamics in CRS-1.

Methods: Post ischemic heart failure was induced in C57 and SCID mice by left anterior coronary artery ligation. Mice were divided in 4 groups: sham, myocardial infarction (MI), MI treated with cobalt protoporphyrin (CoPP), an inducer of HO-1, in the presence and absence of HO activity inhibitor, stannous mesoporphyrin (SnMP). All mice underwent echocardiography (ejection fraction, EF) and renal echoDoppler (arterial pulsatility index, K-PI) examination 30 days after surgery.

Results: EF was significantly reduced both in control and SCID mice after MI (C57: sham 0.60±0.07, MI 0.45±0.04, p<0.05; SCID: sham 0.60±0.06, MI: 0.46±0.1, p<0.01). K-PI was significantly increased in MI groups compared to sham groups (C57: sham 0.98±0.05, MI 1.12±0.11, p<0.05; SCID: sham 0.72±0.08, MI 1.37±0.37, p<0.05). HO1 induction improved renal vasoconstriction only in SCID mice (SCID K-PI: MI+CoPP 0.9±0.19 p<0.5çC57 K-PI: MI+CoPP 1.05±0.15, n.s.). In SCID mice SnMP reversed the effect of CoPP on renal vasoconstriction.

Conclusion: CRS-1 is similar in SCID and control mice and is associated with increased renal arterial resistance. HO-1 induction improves renal vasoconstriction only in SCID (AngII resistant) mice with CRS-1, suggesting that increased HO-1 activity cannot protect the kidney from AngII-induced lymphocyte activation, but only from SNS-induced vasoconstriction.