Sodium Gradient and Renoprival Hypertension in the Rat

Abstract

Following uephrectomy in the rat blood pressure rises while the extracellular fluid volume increases, sodium concentration falls and potassium rises. These changes (without the potassium rise) can be mimicked by simple hyperosmotic loading while the reverse can bo induced by dehydration. The rise in blood pressure is not due to either expansion of the extracellular space or the fall in sodium concentration alone but probably to the resultant decrease in the Na o /Na; gradient.T HE effects of renal extirpation have long been of critical importance to theories of the hypertensive process. Indeed, Goldblatt's original thinking was conditioned by his failure to observe any rise in pressure in the neplvrectomized dog.1 Later, however, BraunMenendez and von Euler 2 noted that blood pressure did in fact rise in the nephrectomized rat and subsequently, Grollman et al. 3 showed that this was also true in the nephrectomized dog kept alive by peritoneal lavage. There is now no argument about the fact, but two opinions as to its explanation. One opinion is that the case for an antipressor function of the kidney in the hierarchy of renal pressor materials has been made. 4 The other suggests that in the absence of renal regulation, salt and water undergo a basic redistribution which is causally related to the hypertension.5 As yet, no specific renal material has been isolated to prove the first case, nor has any electrolyte change been pinpointed to prove the latter.Our immediate interest in the problem steins from the demonstration that smooth muscle tone in general and peripheral vascular tone in particular is directly related to the extra/intracellular gradient of sodium, 6 a view also reached by Eaab and co-workers, 7 from different evidence. The sodium gradient is a dynamic equilibrium, or stead}' state, which can be altered in several basic ways, From the Department of Anatomy, The TJnivorsity of British Columbia, Vancouver, Canada.Supported by a grant from the Ciba Company Ltd., Montreal.Eeceived for publication June 1, 1959. first and probably most simply by a shift of water between the cell and its environment in accord with osmotic requirements, second by an alteration in Donnan forces, third by a change in membrane permeability affecting either inward or outward movement of sodium or both, and fourth, by changes in the metabolically driven sodium transport (extrusion). Seemingly, no matter how caused, a fall in the gradient Na o /Naj results in an increase in tone.In the present report the problem of renoprival hypertension has been restudied and evidence is presented to show that the rise in blood pressure is again a function of a fall in sodium gradient. The emphasis on sodium does not exclude potassium, calcium or other ions, but represents only our present limited point of attack. METHODSAdult male albino rats of an inbred Wistar strain were used throughout. The basic methods for deriving' data concerning the gross extracellular distribution of Na, K and water have been described elsewhere.8 Briefly, inulin...