Demonstration of a Role of Physical Factors as Determinants of the Natriuretic Response to Volume Expansion*

Abstract

Abstract. The importance of plasma protein concentration, renal vascular resistance, and arterial pressure as mediators of the natriuretic response to volume expansion was investigated in anesthetized dogs.Saline loading depressed plasma protein concentration and increased arterial pressure but did not decrease renal vascular resistance. Restoring plasma protein concentration by infusing hyperoncotic albumin increased sodium reabsorption and decreased sodium excretion during saline loading despite simultaneous decreases in renal vascular resistance and increases in arterial pressure.Infusion of "plasma" did not depress plasma protein concentration and produced natriuresis associated with increased arterial pressure and marked decreases in renal vascular resistance. Unilateral hemodynamic natriuresis was produced before "plasma" loading by the renal arterial infusion of acetylcholine, and the subsequent infusion of "plasma" resulted in much smaller increases in sodium excretion by the vasodilated kidney than by the control kidney. If perfusion pressure to both kidneys was then reduced by aortic constriction sodium excretion by the vasodilated kidney could be reduced to preloading (vasodilated) levels without reduced glomerular filtration, despite continued natriuresis in control kidneys which underwent vasodilatation in response to the infusion of plasma.Infusion of equilibrated whole blood did not alter plasma protein concentration or the hematocrit, and renal vascular resistance did not decrease. Sodium excretion was increased minimally or not at all by the infusion of blood despite increased arterial pressure and glomerular filtration. However, in kidneys vasodilated before infusing blood sodium excretion increased in response to tfie infusion in association with increased arterial pressure. This increased excretion of sodium by vasodilated kidneys during infusion of blood could be abolished by reducing perfusion pressure to the preloading level.These observations indicate that changes in plasma oncotic pressure, renal vascular resistance, and arterial pressure either alone or in combination are important variables determining the natriuretic response to volume expansion, and that the relative importance of each of these factors depends on the manner in which volume is expanded (viz., the infusion of saline, plasma, or blood).

Effect of changes in renal perfusion pressure on the suppression of proximal tubular sodium reabsorption due to saline loading

“…With regard to this latter change, they suggested that the distensibility of the proximal tubule might be limited during rapid saline infusion because of an increase in hydrostatic pressure, or a fall in colloid oncotic pressure in the peritubular capillaries, and a resultant increase in interstitial volume proximal tubular volume to GFR/nephron. (26,28,29). The rise in GFR which often occurs in the rat during saline loading would thus not be accompanied by a proportionate increase in the volume of the proximal tubule.…”

“…The precise mechanism by which a rise in peritubular capillary pressure might inhibit proximal sodium transport is unknown. Earley, Martino, and Friedler (26,28,29) have postulated that increases in pressure within the capillaries delay the removal of the tubular reabsorbate, thus causing an increase in the interstitial volume of the kidney. Lewy and Windhager (10) and Nutbourne (33) suggested that an increase in renal interstitial volume might create a layer of high sodium concentration within the basal labyrinth adjacent to the transporting membrane of the tubular epithelium which might then interfere with the active sodium pump mechanism or enhance back-diffusion of sodium into the cells.…”

Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat

“…Hemodynamic and physical factors can also influence salt excretion (25). Koehn, Schindler, and Stanton (26) demonstrataed that aortic perfusion pressure was reduced by approximately 17% in radiothyroidectomized rats; Reville and Stephan (7,19) found an elevated plasma protein concentration in dehydrated hypothyroid rats; and Osorio and Zadunaisky (20) demonstrated that the clearance of Diodrast was decreased by 66% in conjunction with a 33% reduction in the Ctn and resulted in an increased filtration fraction in these animals.…”

Salt and hypertension--future directions.

“…Earlier studies that evaluated COP effects on urine excretion were performed before the discovery of many factors now known to influence sodium excretion and were therefore not well controlled. 27 " 29 Because changes of COP can substantially alter renal excretion, these relations need to be explored in salt-sensitive forms of hypertension.…”