779-4 Biphasic Alterations in Plasma Nitric Oxide in Experimental Progressive Heart Failure

Congestive heart failure (CHF), a syndrome which progresses from a compensated to a decompensated state, is characterized by maintenance of sodium excretion without activation of the renin-angiotensin system (RAS) to a state of sodium retention with an activated RAS. While a role for atrial natriuretic peptide (ANP) in maintaining this initial state of compensation has been advanced, controversy persists with regard to the activity of the endogenous nitric oxide (NO) system in CHF. Such controversy may reflect temporal changes in the endogenous NO system not previously observed. Like ANP, NO also possesses important vasodilatory, natriuretic and renininhibiting actions via activation of cGMP. The objective of the current study was to determine the temporal changes in plasma nitric oxide as determined by chemiluminescence and associated changes in plasma ANP, cGMP, plasma renin activity and sodium excretion. We defined these parameters in a unique canine model of progressive CHF produced by incremental rapid ventricular pacing (180bpm to 240 bpm, n=51 over a 30 day period.Pre-CHFDay 10-CHFDay 25-CHFDay 30-CHFEF53±230±4*24±2*†21±l*†MAP106±2110±5101±494±6*†NO6.8±0.0496±1.110.6±1.4*6.2±0.2ΔANP37±5257±85*574±35*†572±83*†cGMP4.1±0.312.5±09*20.1±2.5*†19.3±2.4*†PRA0.98±0.41.7±0.71.7±087.2±2.2*†ΔUNaV44±442±224±616±9*†*p<0.05 Vs Pre-CHF.Δp<0.05 vs Day 25-CHF.†p<0.05 vs Day 10-CHF.EF, ejection fraction (%); MAP, mean arterial pressure (mmHg); NO, nitrate Inmol/mL); ANp, (pg/mL); cGMP, plasma cGMP(pmol/mL); PRA, plasma renin activity (ng/mL/hrl: UNaV, urinary sodium excretion (mEq/24 hr).These studies demonstrate a unique biphasic response in plasma NO as characterized by an increase in NO during the initial compensated phase of CHF, followed by a decrease with the onset of avid sodium retention and activation of the RAS. These studies provide evidence for NO as a participant in the adaptive changes in the cardiorenal and humoral systems with progressive heart failure