Atrial Natriuretic Factor Infusion following Acute Renal Ischemia in Anesthetized Dogs

Abstract

Atrial natriuretic factor (ANF) has been shown to be effective in reversing renal functional impairments following renal ischemia. We studied the effects of a nonhypotensive intravenous ANF infusion (100ng/min × kg BW, 60 min) after 90 min unilateral renal arterial occlusion in anesthetized dogs with an intact contralateral kidney. ANF plasma levels remained unchanged in controls (group 1) and increased in ANF-infused animals (group 2) from 22 ± 3 to 552 ± 124 pg/ml. Blood pressure increased in both groups during renal ischemia, but returned to control values in group 2 when ANF infusion was started. Plasma vasopressin did not change in groupl, but increased in group 2 (0.77 ± 0.29 vs. 1.10 ± 0.49 pg/ml) after terminating ANF infusion. The postischemic fall in creatinine clearance (C_Cr) filtration fraction (FF) and renal blood flow (RBF) was prevented by infusion of ANF (C_cr: group 1, 0.16 ± 0.05 vs. group 2, 1.01 ± 0.25 ml/min × kg BW; FF: groupl, 4.0 ± 1.6 vs group2, 14.114.1%; RBF: groupl, 6.0 ± 1.2 vs. group 2,9.2 ± 1.6 ml/min × kg BW); however, the effects were limited to the time of infusion and the postischemic increase in urinary excretion of the proximal tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG; group 1, 317.7 ± 163.6 vs. group 2, 672.4 ± 245.7 µU/min × kg BW) was not improved by ANF Our data suggest that infusion of ANF transiently reverses postischemic renal impairment. However, the failure to demonstrate a sustained postischemic improvement of renal functional parameters and to ameliorate massive NAG excretion casts doubt on the benefit of ANF infusion in preventing cellular damage.

Atrial Natriuretic Factors: The Treatment of the Future or a False Hope?

“…Tubular function was also im proved as evidenced by an increase in net tubular sodium rcabsorption. This observation has also been made in dog kidneys [Akabane et al, 1988: Klein et al. 1992].…”

“…In general, most investigators agree that ANP infusion during the postischemic period results in an improve ment in GFR and therefore has significant thera peutic potential [Conger et al, 1989[Conger et al, . 1991Klein et al, 1992: Nakamoto et al, 1987: Pollock and Opgenorth. 1990.…”

Atrial natriuretic peptide infusion improves ischemic renal failure after suprarenal abdominal aortic cross-clamping in dogs

“…At the dose of ANP used in this study, localized renal vasodilation rather than systemic hypotension would be expected. In another dog model with unilateral renal arterial occlusion for 1.5 hrs, ANP infusion for 1 hr after ischemia prevented the decreases in renal clearance and blood flow, the effects of which were only limited during the infusion (17). However, repeated bolus injection of ANP after 2 hrs of renal ischemia in a unilaterally nephrectomized dog model has been reported to ameliorate acute renal failure on the first and second postischemic day (18) so as to maintain sufficient plasma ANP concentrations.…”

Atrial Natriuretic Peptide Has No Potential to Protect Against Endotoxin-lnduced Acute Renal Failure in the Absence of Renal Nerves.

“…The reno-protective effect of ANP during endotoxemia could therefore be traced in the absence of renal nerves, although the improvement in the GFR value was relatively minor, considering the massive pharmacological dose of ANP employed. Recent studies show a therapeutic potential of the ANP for preserving renal function after renal ischemia [8,9]. ANP administration immediately after the ischemic insult significantly improves renal structure and function as assessed by GFR and ATP generation [9,10], the effects of which are not seen with other vasodilators such as acetylcholine [27] and nitroprusside [28].…”

“…Most often, where Et is associated with acute renal failure, it appears to be largely acute tubular necrosis [6,7]. Recent studies have reported beneficial effects of atrial natriuretic peptide (ANP) in limiting ischemic renal injury [8,9]. In animal models of acute ischemic renal damage, ANP decreases renal vascular resistance [8,10], increases renal blood flow [11,12] and consequently, increases GFR [13,14], which suggests a possible hemodynamic action of ANP in recovery from renal injury induced by an Et.…”