A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.

Abstract

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50±11 vs. 158±37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4±2.4 vs. 0.6±0.4 ng/ml per h, P < 0.05) and aldosterone (36.4±12.5 vs. 2.5±0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion

Maximizing the Renal Cyclic 3′-5′-Guanosine Monophosphate System with Type V Phosphodiesterase Inhibition and Exogenous Natriuretic Peptide

“…These findings were surprising in view of improved CO in the PDE VI-treated group. Previous studies demonstrated a compensatory role for the endogenous NP to maintain renal hemodynamic and excretory function in CHF (20). In the PDE VI group, however, there was a strong trend for plasma BNP to be lower as compared with the untreated CHF group.…”

Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

“…Newfoundlands, on the other hand, had low renin activity and high ET‐1 as well as NT‐proBNP concentration 11. Natriuretic peptides are known to suppress RAAS activation in dogs as well as people,32, 33 and ET‐1 has been suggested to inhibit renin production, but the interaction between hormonal systems is complex 34. Taken together, the present results indicate that if ET‐1 and natriuretic peptides are high, the renin activity is low and vice versa.…”

The Treatment of Heart Failure: The Role of Neurohumoral Activation.

“…In an animal model of early left ventricular dysfunction without overt heart failure, plasma norepinephrine levels are elevated, indicative of early SNS activation (2). Power spectral analysis of heart rate variability suggests that there is sympathetic activation early in the course of left ventricular dysfunction in a canine model of heart failure (3).…”