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Journal ArticleDOI

The Role of Renin in the Exaggerated Natriuresis of Hypertension

01 Aug 1970-Circulation (Lippincott Williams & Wilkins)-Vol. 42, Iss: 2, pp 335-345
TL;DR: The enhanced capacity of the renin-unresponsive hypertensive subjects to excrete a salt load suggests either a functionally significant degree of extracellular fluid volume expansion or a direct role for renin in the natriuresis accompanying volume expansion.
Abstract: Hypertensive patients were classified according to their plasma renin response when challenged by the potent diuretics, ethacrynic acid (50 mg IV), or furosemide (40 mg IV), into renin-unresponsive and renin-responsive groups In the latter plasma renin activity rose by at least 05 ng of angiotensin/ml/hr after the diuretic The response to volume expansion with 2 L of isotonic saline infused over 60 min was then studied Peak rate of sodium excretion after saline loading was 994±186 µEq/min in the renin-unresponsive group and peak urine flow was 119 ± 21 ml/min In the renin-responsive hypertensives peak sodium excretion was 448 ± 149 µEq/min and peak urine flow was 54 ± 15 ml/min Both the sodium excretion and urine flow responses were significantly higher (P < 005) in the renin-unresponsive group The degree of saline-induced diuresis and natriuresis was not related to the preexisting level of aldosterone production Plasma renin changed little in either group during saline infusion but tended to
Citations
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Journal ArticleDOI
TL;DR: The affirmative position that the SHR is, indeed, an excellent model for the study of essential hypertension is taken, however, with four important caveats.
Abstract: IN 1963, Okamoto and Aoki introduced a new model of experimental hypertension that required no physiological, pharmacological, or surgical intervention. This spontaneously hypertensive rat (SHR) was developed by meticulous genetic (brother-to-sister) inbreeding that uniformly resulted in 100% of the progeny having naturally occurring hypertensive disease (Okamoto and Aoki, 1963; Okamoto et al., 1966a). Since then, several expert panels have reported that the SHR is an excellent model of experimental hypertension that could serve as a counterpart for clinical essential hypertension (Undenfriend and Spector, 1972; ILAR, 1976). In this discourse we take the affirmative position that the SHR is, indeed, an excellent model for the study of essential hypertension. We do so, however, with four important caveats. First, we recognize that it is unlikely that both forms of naturally occurring hypertension (man and rat) are identical expressions of genetically determined hypertensive disease. Second, we take the position that both forms of hypertension are polygenic in origin and that both are influenced by environmental factors. Thirdly, since the control of normal arterial pressure in both man and rat is multifactorial, it follows that certain pressor mechanisms might well operate in one form of genetic hypertension that do not necessarily occur in the other (although in both, some similar factors could be involved). This same reasoning also may be applied to hypertensive in-

511 citations

Journal ArticleDOI
TL;DR: Dahl's original hypothesis, that the kidney's control of sodium excretion is paramount in the control of blood pressure, is used to form a possible explanation for the origins of essential hypertension.

393 citations

Journal ArticleDOI
TL;DR: The role of the kidney in blood-pressure regulation was established by TIGERSTEDT and Bergman at the close of the 19th century as discussed by the authors, who produced hypertension in dogs by injecting a cr...
Abstract: TIGERSTEDT and Bergman established a role for the kidney in blood-pressure regulation at the close of the 19th century. In a classic experiment, they produced hypertension in dogs by injecting a cr...

278 citations

Journal ArticleDOI
TL;DR: Critical issues will be addressed are whether this represents a volume expansion type of hypertension; whether an unidentified mineralocorticoid accounts for this syndrome; what, if any, its prognostic implications are; and how it should be treated.

164 citations

Journal ArticleDOI
TL;DR: Compared with normotensive volunteers studied previously under the same conditions, the hypertensive subjects had a greater response in urine volume and sodium, calcium, and magnesium excretion but a less sustained fall in arterial pressure.
Abstract: Because there is little published information on the effects of atrial peptides in hypertensive humans, 100 micrograms of alpha-human atrial natriuretic peptide was injected intravenously into six patients with essential hypertension in a double-blind, placebo-controlled study under standardized conditions of body posture and dietary sodium and potassium intake. The peptide increased urine sodium excretion sixfold in the first 30 minutes. Smaller increments occurred in urine volume and in calcium, magnesium, and phosphorus excretion; the rise in urine potassium concentration was not statistically significant. Most of these indices returned to time-matched placebo values within 1 hour, but urine sodium excretion remained high for 2 1/2 hours. Arterial pressure fell within 2 minutes of alpha-human atrial natriuretic peptide injection, then returned to matching placebo levels by 10 minutes. Conversely, heart rate increased rapidly and remained elevated for 3 hours. The peptide induced a prompt, brief rise in plasma norepinephrine concentration and a more sustained fall in epinephrine and aldosterone levels, but it did not affect plasma renin activity or cortisol concentration. Compared with normotensive volunteers studied previously under the same conditions, the hypertensive subjects had a greater response in urine volume and sodium, calcium, and magnesium excretion but a less sustained fall in arterial pressure.

135 citations


Cites result from "The Role of Renin in the Exaggerate..."

  • ...In this regard it is interesting to note that the natriuretic response to furosemide (with which atrial peptides have been compared) is by contrast the same or less in hypertensive patients compared with that in normotensive subjects.(13)"(15) Second, the hypertensive subjects had little or no fall in arterial pressure apart from the brief hypotensive response immediately after a-hANP injection....

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References
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Journal ArticleDOI
TL;DR: It is suggested that both upright posture and sodium depletion lead to decreases in effective plasma volume and increases in sympathetic nervous system activity, which is responsible for an increase in renal afferent arteriolar constriction, leading to a increase in renin secretion and, ultimately, an increaseIn aldosterone secretion.
Abstract: Several lines of evidence have been developed indicating that the sympathetic nervous system may play a role in mediating the renal and adrenocortical secretory responses to upright posture and sodium deprivation. Despite concurrent increases in arterial blood pressure, the plasma renin activity of normal subjects increased both in response to the infusion of catecholamines (norepinephrine: epinephrine, 10:1) and in response to stimulation of the sympathetic nervous system by cold. Aldosterone excretion was also increased by catecholamine infusion. In normal subjects the stimuli of upright posture and of sodium depletion both resulted in increases in urinary catecholamines, plasma renin activity, and urinary aldosterone. A patient with severe autonomic insufficiency did not experience normal elevations of urinary catecholamines, plasma renin activity, or urinary aldosterone in response to upright posture or sodium deprivation, despite a substantial fall in arterial blood pressure. When orthostatic hypotension was prevented by infusion of catecholamines, however, increases in plasma renin activity and in aldosterone excretion were observed. We suggest that both upright posture and sodium depletion lead to decreases in effective plasma volume and increases in sympathetic nervous system activity. This increase in sympathetic activity is then responsible for an increase in renal afferent arteriolar constriction, leading to an increase in renin secretion and, ultimately, an increase in aldosterone secretion.

306 citations

Journal ArticleDOI
19 Oct 1964-JAMA
TL;DR: It is now clear that, when hypersecretion of aldosterone occurs in human renal hypertension (secondary aldosteronism), it is the result of increased activity of the renin-angiotensin system.
Abstract: THE OCCURRENCE in a hypertensive patient of increased production of aldosterone, and of the hypokalemia which often accompanies it, is due either to the presence of an aldosterone-secreting adrenocortical tumor (primary aldosteronism), or the presence of a functional renal hemodynamic change which stimulates the renal juxtaglomerular cells to secrete into the blood abnormally large amounts of renin In the latter case, an increased quantity of angiotensin II is thus generated Angiotensin II has been established to be a potent stimulus for the secretion of aldosterone by the adrenal cortices of man1,2Although increased secretion of aldosterone can be induced in man by other mechanisms, it is now clear that, when hypersecretion of aldosterone occurs in human renal hypertension (secondary aldosteronism), it is the result of increased activity of the renin-angiotensin system This seems to be true whether the decreased "stretch"3at the renal baroreceptor site (the juxtaglomerular cells)

285 citations

Journal ArticleDOI
TL;DR: A mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR is suggested by suggesting the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb.
Abstract: Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10−6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.

243 citations

Journal ArticleDOI
TL;DR: From the results of this study one might infer either that some unidentified mineralocorticoid is present in excessive quantities in the patients with suppressed plasma renin activity or that even normal levels of aldosterone are normal in patients with essential hypertension.
Abstract: Patients with essential hypertension can be divided into subpopulations according to their plasma renin values. Approximately 80% have normal or near-normal plasma renin values while 20% have distinctly subnormal renin values in response to the double stimuli of upright posture and sodium depletion. In the present study, nine patients with suppressed renin activity were compared with five patients with normal renin values in search of other physiologic differences that might shed light on the pathophysiology of the hypertensive state. Hypertensive patients with suppressed renin activity differed from those with nonsuppressed renin activity in two respects: They had significantly higher exchangeable sodium values, and they responded to the adrenal inhibitor, aminoglutethimide, with significant decreases in blood pressure. From the results of this study one might infer either that some unidentified mineralocorticoid is present in excessive quantities in the patients with suppressed plasma renin activity or that even normal levels of aldosterone

185 citations