Renal function after myocardial infarction and cardiac arrest in rats: role of ANP‐induced albuminuria?

Abstract

Renal function was measured by clearance technique before and after acute myocardial infarction (MI) induced by left coronary artery ligation in male Sprague-Dawley rats. The animals were anaesthetized with halothane-nitrous oxide, paralysed with pancuronium and artificially ventilated. All parameters were stable throughout the experiment in sham-operated time control animals (n = 8). After MI, rats developed left ventricular dysfunction with increased left ventricular end-diastolic pressure and decreased mean arterial pressure. MI produced antidiuresis and antinatriuresis without changes in glomerular filtration rate (GFR), lithium clearance or renal albumin excretion (n = 8). The antidiuretic and antinatriuretic responses to MI were similar in rats with chronic bilateral renal denervation (n = 5). Three additional rats with chronic bilateral renal denervation had cardiac arrest and were resuscitated with cardiac massage, i.v. lidocaine and intracardiac adrenaline administration. These animals showed a transient increase in urine flow rate, sodium and albumin excretion with maximum 30-60 min after resuscitation, while GFR and lithium clearance were normal. Since cardiac ischaemia and sympathetic stimulation are strong stimuli for the release of atrial natriuretic peptide (ANP), we examined if ANP (0.25, 0.50, and 1.00 microg kg(-1) min(-1), n = 8 per dose) affects urinary albumin excretion. ANP increased dose-dependently the urine/plasma concentration ratio of albumin relative to inulin, which suggests that ANP increases the glomerular permeability for albumin. We conclude that MI causes stimulation of renal tubular sodium and water reabsorption by a mechanism which is independent of intact renal innervation. MI does not produce any change in renal albumin excretion in rats, but transient albuminuria may be observed in rats following cardiac arrest and/or manoeuvres used in cardiac resuscitation. Since ANP produces albuminuria, we speculate that ANP may be an important mediator of albuminuria in states with elevated plasma concentrations of ANP.

Transient and sustained increases in glomerular permeability following ANP infusion in rats

“…Previous studies have indeed demonstrated that systemic ANP infusion in anesthetized rats can markedly increase urinary albumin excretion, although the exact mechanisms of this proteinuric action have not been elucidated (22). The direct assessment of glomerular permeability in the present study supports the concept that ANPinduced albuminuria is a consequence of a direct effect on the glomerular filtration barrier, leading to a partly reversible increase in the radius and number of large glomerular pores without any primary effects on glomerular charge selectivity.…”

“…From the data of Tucker et al (34), we could calculate that an iv ANP infusion rate of 800 ng·kg Ϫ1 ·min Ϫ1 would produce a plasma concentration of 1,740 pg/ml, which is in the (lower) range of 2,000 -3,000 pg/ml, which have been observed after 25% blood volume expansion in rats with experimental heart failure (10), but higher than observed after 20% plasma volume expansion in rats by another group (24). Furthermore, 800 ng·kg Ϫ1 ·min Ϫ1 is about intermediate between the medium and the high doses of ANP infused in rats for studies of ANP-induced albuminuria by Nielsen et al (22).…”

“…In the latter conditions, microalbuminuria has been attributed to permeability effects mediated via ANP. Intravenous (iv) infusion of ANP in anesthetized rats thus resulted in moderate increases in urinary albumin/Inulin concentration ratios for the dose of 0.5 g·min Ϫ1 ·kg Ϫ1 body wt (BW) and in marked albuminuria for a dose of 1 g·min Ϫ1 ·kg Ϫ1 (22). The exact (patho)physiology of ANP-induced albuminuria is not known.…”

Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways

“…The protective effect of OT is first attributable to its negative chronotropic and inotropic roles in cardiac activity following the activation of cardiac OTR (Costa E Sousa et al, 2005) in association with the release of protective atrial natriuretic peptide (ANP) and nitric oxide (NO) (Houshmand et al, 2015) and increase in parasympathetic output (Sun et al, 2015), decrease in the activity of renin-angiotensin-aldosterone system (Nielsen et al, 1997) and reduction of sympathetic outflow (Olszewski et al, 2010). In addition, OT also decreased cardiac preload and afterload through its diuresis and natriuretic effect (Nielsen et al, 1997). As a result, OT can reduce oxygen consumption while increasing the cardiac output during I/R injury.…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…In our studies, surgical denervation produces a consistent reduction of renal norepinephrine concentration of this magnitude (V; Spannow et ul. 1997;Nielsen et al 1997).…”