The effect of renin on urine formation1

Pickering, George; Prinzmetal, Myron

doi:10.1113/jphysiol.1940.sp003852

Cited by 87 publications

(24 citation statements)

References 7 publications

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“…All such proposed units are Variations of the same procedure whether dogs (11,12,17,18,19), cats (17), or rabbits (14) are used.…”

Section: Kinetic Analysis Op Renin-angiotonin Pressor Systemmentioning

confidence: 99%

A Kinetic Analysis of the Renin-Angiotonin Pressor System and the Standardization of the Enzymes Renin and Angiotonase

Plentl¹,

Page²

1943

Journal of Experimental Medicine

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Sufficient is now known of the renal vasopressor system and its relationship to the mechanism of hypertension to justify a more exacting analysis of it. Shortly after the discovery of angiotonin it was noted that when renin and plasma were allowed to interact, angiotonin at first increased and then slowly began to decrease (3). We had no evidence at that time as to the nature of the decrease, and it was merely suggested that angiotonin was an intermediate rather than an end product in these closely associated reactions. This has proved to be true, and the catalyst causing the further breakdown was shown by Fasciolo, Leloir, and Mufioz (20,4) to be an enzyme denominated hypertensinase by them. In line with the nomenclature employed by us (22, 23) this becomes "angiotonase."Good evidence had suggested that the reaction between renin and reninsubstrate is enzymatic, but proof that this is so came from a recent kinetic analysis of the problem demonstrating the reaction to be of the first order (1). Since both physiological and chemical investigation of renin depends on the ability to assay it quantitatively, we have sought such a method.The methods of bioassay of renin have recently been summarized by Goldblatt, Katz, Lewis, and Richardson (11) in a paper in which they described a method of assaying renin which does not differ appreciably from some previously reported. They overlooked an important contribution by Leloir et al. (5) in which there is proposed a renin unit based upon the amount of pressor substance (anagiotonin) formed. The method of Goldblatt, Katz, Lewis, and Richardson and previous methods referred to by them, are based upon the determination of the rise in arterial pressure elicited by intravenous injection of given amounts of renin solution. Since renin itself is not a pressor substance, it should not be tested for its pressor but for its enzymatic action; that is, in terms of renin-substrate decomposed or angiotonin formed. Similar arguments apply to destruction of angiotonin by angiotonase. A satisfactory method for the assay of angiotonase has been described by Page and Helmer (21).Since kidney extracts usually contain both renin and angiotonase the assay of renin becomes difficult because angiotonase interferes with the determination

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“…All such proposed units are Variations of the same procedure whether dogs (11,12,17,18,19), cats (17), or rabbits (14) are used.…”

Section: Kinetic Analysis Op Renin-angiotonin Pressor Systemmentioning

confidence: 99%

A Kinetic Analysis of the Renin-Angiotonin Pressor System and the Standardization of the Enzymes Renin and Angiotonase

Plentl¹,

Page²

1943

Journal of Experimental Medicine

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“…The RAAS is involved in the regulation of blood volume and systemic vascular resistance, which together regulate blood pressure (Bogatzki, 1964;Conn, et al, 1965;Mulrow and Ganong, 1962;Nahum, 1965a;Nahum, 1965b;Tigerstedt and Bergman, 1898). Drugs targeting the RAAS (angiotensin I-converting enzyme (ACE) inhibitors or angiotensinogen II receptor type 1 antagonists) have been shown to reduce hypertension and decrease proteinuria (Collier, et al, 1973;Gavras, et al, 1974;Pickering and Prinzmetal, 1940) with a concomitant reduction in rate of renal injury in chronic kidney disease. These drugs have been shown to be effective, with a range of effects, in a majority of patients (Corvol and Plouin, 2002;Croog, et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Functional genetic variation in aminopeptidase A (ENPEP): Lack of clear association with focal and segmental glomerulosclerosis (FSGS)

Tonna

Dandapani

Uscinski

et al. 2008

Gene

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The aminopeptidase A (APA) ectopeptidase is an integral membrane-bound zinc metalloprotease that cleaves aspartic and glutamic acidic residues from the N-terminus of a number of protein substrates that includes angiotensin II. Angiotensin II, the most vasoactive component of the reninangiotensin-aldosterone (RAAS) pathway, can contribute to renal disease by causing an increase in arterial blood pressure leading to glomerular injury and fibrosis. APA is expressed in many organs, including the kidney where it localizes mainly to the podocyte cell membrane and brush borders of the proximal tubule cells. Antibodies directed to the APA peptide can induce an acute massive albuminuria in wild type BALB/c mice after intravenous injection.We examined whether variants in the APA encoding gene (ENPEP) are more frequent in individuals with the proteinuric disease focal and segmental glomerulosclerosis (FSGS) compared to control individuals. The ENPEP coding sequence was resequenced in 188 FSGS patients and 48 controls. Genetic variants were further genotyped in 181 individuals without any known kidney disease. We then examined the effect of the non-synonymous coding variants identified on their cell surface APA activity after transfection in COS-1 cells.Several of these ENPEP variants lead to reproducibly altered APA activity. However, we did not see a clear correlation between the presence of a functional ENPEP variant and FSGS. However, the existence of these variants with marked effect on APA activity suggests that both rare and common variation in ENPEP may contribute to the development of renal and hypertensive disorders and warrants further study.

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“…A much more careful quantitative comparison is needed. Pickering & Prinzmetal (1940) and Hughes-Jones et al (1949) suggested that the diuretic action of renin was not a pressure diuresis but was due to a direct action on the renal tubular capacity differentially to re-absorb water, sodium and chloride. With large doses of renin, urine flow and creatinine clearance were diminished during the period of greatest rise of pressure; the diuresis occurred after the main pressor effect and tended to outlast it; glomerular filtration rate was not constantly changed, nor was the ratio creatinine clearance/glucose Tm.…”

Section: Discussionmentioning

confidence: 99%

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mentioning

confidence: 99%

The action of synthetic angiotensin on renal function in the unanaesthetized rabbit

Langford¹,

Pickering²

1965

The Journal of Physiology

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In the rabbit, renin was observed to increase conspicuously the rate of urinary excretion of water, sodium and chloride (Pickering & Prinzmetal, 1940). A detailed analysis showed that the first effect of renin was to reduce urine flow and that this was the chief effect of small doses. With increasing doses, the period of reduced urine flow was followed by one in which the urine flow increased to values much higher than those obtained during water diuresis. The urine was peculiar in containing protein and having a sodium and chloride content approximate to, and tending slightly to exceed, that of the plasma. The effect persisted during successive phases of purification of renin, was destroyed by boiling, which destroys renin, and was absent from similar preparations of liver which contained no renin.In 1949 Hughes-Jones, Pickering, Sanderson, Scarborough & Vandenbroucke showed that angiotensin prepared by incubating ox plasma and rabbit renin had a similar effect. They made a fuller analysis using inulin and diodone clearances and Tmn, and concluded that the diuretic action was probably to be explained by a direct effect of angiotensin on the tubular capacity differentially to re-absorb water and sodium chloride. Because the urine levels of chloride tended to exceed plasma and to approximate to those observed by Walker, Bott, Oliver & McDowell (1941) in proximal tubular urine, they suggested that the effect of angiotensin might be on the distal tubule.

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The effect of renin on urine formation1

Cited by 87 publications

References 7 publications

A Kinetic Analysis of the Renin-Angiotonin Pressor System and the Standardization of the Enzymes Renin and Angiotonase

A Kinetic Analysis of the Renin-Angiotonin Pressor System and the Standardization of the Enzymes Renin and Angiotonase

Functional genetic variation in aminopeptidase A (ENPEP): Lack of clear association with focal and segmental glomerulosclerosis (FSGS)

The action of synthetic angiotensin on renal function in the unanaesthetized rabbit

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