Renin and Acute Circulatory Renal Failure in the Rabbit

Abstract

Plasma renin concentration (PRC) was measured in 25 rabbits before and 6, 24, or 72 hours after subcutaneous injection of glycerol. Renal failure and tubular necrosis developed in most animals and PRC rose sixfold to a maximum at 24 hours. Small insignificant changes of PRC were present at 6 and 72 hours. None of these changes was observed in a control group of nine animals killed 24 hours after an injection of saline. The amount of renin extractable from single superficial glomeruli and from renal cortical tissue was reduced after injection of glycerol. In a second study of 11 anesthetized rabbits, renal venous PRC increased on average from 151 to 1810 units/liter following a 4-hour period of renal artery occlusion. Arterial PRC did not change significantly during this time, but the kidneys showed histological changes of acute tubular necrosis. These experiments are compatible with the suggestion that renin is involved in the pathogenesis of acute circulatory renal failure. KEY WORDSglomerular renin glycerol-induced renal failure acute tubular necrosis angiotensin renal artery occlusion• Vasoconstriction within the kidney, particularly in the outer layers of the cortex, is held to be important in the pathogenesis of acute renal failure (ARF) (1, 2). Renin is stored mainly in the outer layers of the renal cortex (3, 4) and, like the plasma or blood levels of renin, renin activity and angiotensin are often increased during the early stages of ARF in man (5-10) and may, by their vasoconstrictor effect, play some part in producing the condition (9, 11). However, analysis of results in man is compromised by lack of information on changes in renin in the early stages of ARF (9). In the first group of experiments reported here, therefore, plasma renin concentration was measured in rabbits before and during the development of ARF produced by glycerol.From the MRC Blood Pressure Unit and the Department of Pathology, Western Infirmary, Glasgow, W.I., Scotland.Received April 2, 1971. Accepted for publication September 27, 1971.The second question investigated was the extent to which levels of renin in peripheral plasma reflect those within the kidney under conditions, such as in ARF, in which renal blood flow is reduced. It is known, for example, that renal venous plasma renin concentration is inversely related to renal blood flow (12). In a second series of rabbits, therefore, the renal artery was occluded for a period sufficient to produce ischemic changes within the kidney, and renin was measured in samples of arterial and renal venous plasma taken before, during, and after the occlusion.A brief account of some of these results has been given recently (13). Methods A. ACUTE RENAL FAILURE PRODUCED BY GLYCEROLForty-nine rabbits were given the acidifying diet described by Lalich (14) to increase susceptibility to ARF (15), which in preliminary experiments had proved difficult to produce. Within 3 weeks, urine pH had decreased from 6.9 or more to 5.5 or less in all animals. Drinking water was then withheld, and aft...

Serial Studies of the Renin System in Rats with Glycerol-Induced Renal Failure

“…The present experiments confirm previous findings of increased activity of the renin sys tem in glycerol-induced renal failure [3][4][5]23]. Initially, changes in the enzyme concentration and later, as renal failure progressed, changes in substrate concentration were largely re sponsible for sustaining the increased activity of the system.…”

“…However, PRC was not increased in our experiments during this period and PRA was initially not increased in their study, at a time when renin-substrate concentration was already significantly de creased [23], So, substrate consumption by circulating renin docs not seem to be the ex planation. Intrarenal destruction of substrate by renal renin is unlikely as the pattern of change in renal renin content is highly variable in the same experimental model of ARF, being decreased in the rat [5] and high [23] or low [4] in the rabbit following glycerol administra tion. There is no reason to believe that there was a sudden decrease in substrate formation, which, in any case, would not have produced such prompt and profound effects on the cir culating pool [25].…”

The Effect of Indomethacin and Prostaglandin (PGE2) on Renal Failure Due to Glycerol in Saline-Loaded Rats

“…Ayer et al (1972) showed that renal plasma flow and glomerular filtration rate decreased during glycerol-induced acute renal failure and concluded that renal failure in this experimental model is due to a primary decrease in glomerular filtration rate resulting from an increased pre-glomerular resistance. Brown et al (1972) and Powell-Jackson et al (1972) suggested that the renin-angiotensin system may be responsible for this and is probably involved in the pathogenesis of ischaemic acute renal failure. The above suggestion is in agreement with the protection afforded by saline infusion against acute renal failure (Wilson et al, 1967.…”

“…The mechanism responsible for the increase in pre-glomerular resistance is not fully understood but among the factors that have been implicated in the afferent arteriolar contraction are the renin-angiotensin system, renal nerves, circulating catecholamines and other vasoactive mediators (Brown, Brown, Gavras, Jackson, Lever, McGregor, MacAdam & Robertson, 1972;Kokot & Kuska, 1969;Oken et al, 1966;Ayer et al, 1971 ;Powell-Jackson, Brown, Lever, McGregor, MacAdam, Titterington, Robertson & Watte, 1972).…”

Measurement of Urinary Renin Activity by Radioimmunoassay: Sequential Studies in Acute Renal Failure in Man

“…ARF has been shown to be associated with renal cortical ischemia and impaired filtration [1,3,17-21], Although several lines of investi gation indirectly implicate the renin-angioten sin system as a possible mediator of these hemodynamic changes [2,4,[22][23][24], the re sponsible mechanisms remain to be estab lished. A role for renin in ARF was first sug gested by Goormaghtigh's [25] studies in 1945, which showed increased j uxtaglomerular activ ity in patients with ARF caused by crush in juries.…”