Assessment of atrial natriuretic peptide resistance in cirrhosis with head-out water immersion and atrial natriuretic peptide infusion

Abstract

The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic action of atrial natriuretic peptide (ANP) may play a potential role in this sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underwent head-out water immersion (HWI) for 3 h and were infused with a alpha-human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HWI, sufficient to achieve negative sodium balance, and these patients were termed responders. Each of these five patients also displayed a natriuretic response to ANP infusion. In contrast, the other seven patients (nonresponders) consistently failed to develop a natriuretic response to either maneuver. The two groups had similar elevations in plasma ANP concentrations, but at baseline differed in terms of plasma sodium, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium than responders during the peak effect of the interventions, suggesting greater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodium excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium delivery to the medullary collecting duct and inhibit the natriuretic effect of ANP at that site.

Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites

“…kidney; sildenafil; viagra; ANP; renin A RELATIVE RESISTANCE TO THE natriuretic action of atrial natriuretic peptide (ANP) has been observed in sodium-retaining conditions such as nephrotic syndrome (40), congestive heart failure (35), and, in particular, cirrhosis of the liver. In liver cirrhosis the normal natriuretic effect of endogenous ANP or exogenously administered ANP 99 -126 is blunted (12,22,33,42). This phenomenon cannot be explained by the existence of a modified or less biologically active peptide in cirrhosis (17,38).…”

“…In liver cirrhosis the normal natriuretic effect of endogenous ANP or exogenously administered ANP 99 -126 is blunted (12,22,33,42). This phenomenon cannot be explained by the existence of a modified or less biologically active peptide in cirrhosis (17,38).…”

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis

“…Specific AEs ( ) were reported in five of the included trials[ 16 , 24 , 34 , 36 , 37 ]. Three studies stated that AEs were absent[ 12 , 25 , 26 ], while no information on AEs was provided by 14 studies[ 11 , 13 - 15 , 22 , 23 , 27 - 33 , 35 ]. The most frequently reported AEs were facial flushing and hypotensive episodes.…”

“…Fyhrquist et al [ 40 ] were the first to report on the natriuretic and diuretic effects induced by intravenous ANP in refractory cirrhotic ascites and in the following decades further investigations with natriuretic peptides administered to cirrhotic patients were conducted. However, the trials sought primarily to elucidate the pharmacodynamics of natriuretic peptides in patients with cirrhosis and ascites, and some used ANP responsiveness to select eligible patients for other experiments e.g., combined treatment of ANP and norepinephrine to stabilize blood pressure[ 33 ], compare ANP responsiveness with responsiveness to head-out water immersion[ 25 ], compare ANP responsiveness with sympathetic nerve activity[ 13 ], test the inhibitory potential of Angiotensin-II on ANP responsiveness[ 28 ], and compare ANP responsiveness before and after establishment of a peritoneovenous shunt[ 29 ]. Thus, the general limitations of the trials are the small number of participants, different study designs, short-term interventions, varying treatment doses, and differences in ascites severity of participants.…”