© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Temporal changes in natriuretic and antinatriuretic systems after closure of a large arteriovenous fistula
aDepartment of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9649, 31096 Haifa, Israel
bDepartment of Vascular Surgery, Rambam Medical Center, P.O.B. 9602, 31096 Haifa, Israel
* Corresponding author. Tel.: +972-4-854-3119; fax: +972-4-852-0751 a_hofman{at}rambam.health.gov.il
Objective: Surgical closure of a large arteriovenous (A–V) fistula in patients and animals is associated with prompt diuresis and natriuresis. However, the mechanisms underlying these changes remained largely unknown. Methods: The present study evaluated the hormonal balance between major antinatriuretic systems (plasma renin activity, PRA, and arginine vasopressin, AVP) and natriuretic systems (atrial natriuretic peptide, ANP, and renal nitric oxide, NO) in Wistar rats with an A–V fistula (1.2 mm O.D., side to side) between the abdominal aorta and inferior vena cava. Results: The placement of an A–V fistula caused progressive sodium retention (UNaV decreased from 1500 to 100 µequiv./day), a significant drop in mean arterial blood pressure (MAP) from 127±3 to 75±2 mmHg (P<0.01), and a significant increase in ANP (from 94±12 to 389±135 pg/ml, P<0.05), PRA (from 22.1±2.0 to 47±14 ng angiotensin I [Ang I]/ml/h, P<0.05), AVP (from 14.2±3.6 to 37.7±9.6 pg/ml, P<0.05), norepinephrine (from 184.2±40.5 to 1112.6±293.2 pg/ml, P<0.05) and epinephrine (from 667.5±175.9 to 2049.8±496.9 pg/ml, P<0.05). Furthermore, these changes were associated with a 3-fold increase in the renal medullary immunoreactive levels of endothelial NO synthase (eNOS), an endogenous vasodilator that plays an important role in the regulation of medullary blood flow. After 6 days, rats with A–V fistula and maximal sodium retention underwent surgical closure of the A–V fistula. The A–V fistula closure was associated with dramatic natriuresis (UNaV=2563±78 and 1918±246 µEq/day on days 3 and 6 following the closure, respectively) and restoration of MAP to normal levels (111±6 mmHg); PRA decreased to 29±5 ng Ang I/ml/h, AVP to 20.3±7.1 pg/ml, and medullary eNOS declined to basal levels, whereas plasma ANP concentrations remained elevated (380±90 pg/ml) after 3 days and returned to normal (92±12 pg/ml) on day 6. Conclusions: These results demonstrate that the creation of A–V fistula is associated with activation of both natriuretic and antinatriuretic systems. Closure of A–V fistula is characterized by shifting the balance in favor of the natriuretic substances. Moreover, the observed alterations in medullary eNOS following the creation and closure of A–V fistula suggest that this system, an important determinant of medullary blood flow, may contribute significantly to the regulation of sodium excretion in this model.
KEYWORDS Anti-hypertensive/diuretic agents; Heart failure; Natriuretic peptide; Renin–angiotensin system; Vasoactive agents; Blood pressure
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