Abstract 15362: Elevated Systemic and Renal cGMP May Contribute to Preserved Cardiovascular Homeostasis in a Large Animal Model of Mild Renal Insufficiency Induced by Uninephrectomy: Relevance to Renal Donation and Cardioprotective Strategies
Objectives: Acute experimental reduction in renal mass produced by uninephrectomy (UNX) leads to reduced CO and increased SVR yet long-term cardiovascular homeostasis following UNX has been associated with relatively preserved homeostasis yet by mechanisms which remain undefined. We aimed to define chronic cardiovascular and renal adaptation in a large animal model of mild renal insufficiency (RI) induced by UNX with the goal of advancing possible cardioprotective strategies in the setting of UNX commonly associated with renal donation.
Hypothesis: We hypothesized that chronic experimental UNX is associated with preserved cardiovascular homeostasis in association with activation of the cGMP second messenger system linking to both the NO and natriuretic peptide guanylyl cylase (GC) receptor systems.
Methods: Dogs were assigned to UNX (n=6) or sham operation (n=6). Echocardiography was performed at baseline and after 12 weeks. At 12 weeks cardiovascular and renal functions were assessed invasively. Data are presented as mean±SD, * indicates p<0.05.
Results: UNX dogs had increased left kidney (LK) weight at 12 weeks (80±10 vs. 59±5g, *) as well as increased LK GFR (59±11 vs. 41±6 mL/min, *). There were no differences between groups regarding MAP, PAP, PCWP, CO and SVR, and diastolic and systolic functions were unaltered in both groups 12 weeks after surgery. Plasma aldosterone, BNP and ANP were not different after 12 weeks, however plasma cGMP was higher in the UNX dogs (6.2±1.2 vs. 4.6±1 pmol/mL, *). LK urinary cGMP excretion was increased in the UNX dogs (1132±325 vs. 667±121 pmol/min, *) ascribable to a trend for increased renal generation of cGMP (UNX 777±345 vs. sham 475±112 pmol/min, p=0.07) as well as the higher plasma level, indicative of activation of the GC signaling cascade in the UNX dogs.
Conclusion: Experimental mild RI induced by UNX in a large animal is characterized by preservation of cardiovascular function after 12 weeks adaptation to reduced renal mass. Importantly however, activation of a cardiorenal protective pathway by activated cGMP is present, and possibly mediates the preserved cardiovascular and renal function and may represent a potential therapeutic strategy for cardioprotection in early chronic RI warranting further studies.
- © 2012 by American Heart Association, Inc.