Rôle of the Kidney in Pathogenesis of Hypertension as Determined by a Study of the Effects of Bilateral Nephrectomy and Other Experimental Procedures on the Blood Pressure of the Dog

Grollman, Arthur P.; Muirhead, E. E.; Vanatta, John C.

doi:10.1152/ajplegacy.1949.157.1.21

Cited by 157 publications

(31 citation statements)

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“…Although most current studies of experimental hypertension are done on renal, mineralocorticoid, or genetic models, the following experimental models of this disease have each added to our knowledge of hypertension: 1) renoprival, 14 2) adrenal regeneration, 15 3) adrenocorticotropic hormone, 16 4) neurogenic, 17 5) psychosocial, 18 and 6) angiotensin II-salt.…”

Section: -40mentioning

confidence: 99%

Experimental hypertension.

Bohr¹,

Dominiczak²

1991

Hypertension

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Several interventions are used to induce hypertension in the experimental animal. The three most used interventions are renal ischemia, mineralocorticoid excess, and genetic manipulation. The sequence of events leading from these initiating manipulations to the elevated arterial pressure is being explored to define the mechanism responsible for hypertension. The following mechanisms are currently extensively evaluated: Pressor and depressor factors of renal origin, neurogenic regulation, circulating humoral factors, vessel wall hypertrophy, and membrane transport abnormality. The experimental models of hypertension hold great promise in providing an understanding of the mechanisms and developing effective treatment in clinical hypertension. (Hypertension 1991;17[suppl I]:I-39-I-44) W ith over 30,000,000 cases of hypertension in the United States, opportunity for clinical research is unlimited. Yet a major source in understanding this disease comes from the use of experimental models of hypertension. Evidence for the magnitude of the contribution made by experimental hypertension is seen in the number of articles published in the past 2 years in our two major journals on hypertension. In 1987 and 1988, Hypertension published 118 clinical and 166 experimental articles, and the Journal of Hypertension published 113 clinical and 108 experimental articles. Based on these data, 54% of our information about hypertension is derived from experimental studies.Historically, "The greatest single advance in the experimental production of the condition resembling that of hypertension in man was a convincing demonstration by Goldblatt, Lynch, Hanzel, and Summerville that persistent hypertension could be produced in dogs" (Sir George Pickering).1 In 1934, Goldblatt et al 2 showed that partial constriction of the renal artery and removal of the opposite kidney produce persistent hypertension (one-kidney, one clip hypertension [1K1C]) in dogs. Differing from dogs, the constriction of one renal artery in rats results in hypertension regardless of the presence or absence of the contralateral kidney. The third major model of experimental hypertension was introduced by Smirk and Hall 6 in 1958, when they developed a colony of hypertensive rats by breeding rats with above-average tail blood pressure. This strain of genetically hypertensive rats is now known as the New Zealand strain.As with mineralocorticoid hypertension, the major impetus for the study of genetic hypertension came later. In 1963, Okamoto and Aoki 7 introduced the spontaneously hypertensive rat (SHR), which is presently the most studied experimental model of hypertension. These investigators commenced their colony by mating a male Wistar-Kyoto (WKY) rat that had elevated blood pressure (145-175 mm Hg) with a female WKY rat that had slightly higher than average blood pressure (130-140 mm Hg). In the Fj and subsequent generations, they conducted brothersister inbreeding of the siblings selected for having the highest pressures in each litter. After the third generation,...

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Section: -40mentioning

confidence: 99%

Experimental hypertension.

Bohr¹,

Dominiczak²

1991

Hypertension

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“…In point of fact, these same experiments usually show a fall in plasma sodium, as might be expected from the preceding analysis. Orbison et al 3 have emphasized, however, that a tenuous equilibrium does exist even where the dog is in apparent balance, by showing that an extreme pressor response may be obtained by expanding the extracellular space. This tallies with our findings in the rat.…”

Section: Experiments 6 Effect Of Sodium On the Blood Pressure Responsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

Sodium Gradient and Renoprival Hypertension in the Rat

Friedman

Nakashima

1959

Circulation Research

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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...

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“…made the following modifications. (Sir fications have recently been reported I [15] and Grollman [16] Since turbulence in the blood circuit contributes to clotting, it was important that this factor be eliminated in so far as was possible. After considerable experimentation, a simple and effective pump was devised by suspending a loop of Tygon tubing in the shape of a narrow, inverted U.…”

Section: Introductionmentioning

confidence: 99%