The morphology of serotonin‐induced renal lesions in the rat

Abstract

The progress of serotonin-induced renal lesions was studied over a period of 6 mth following a single intraperioneal injection of 40 mg/kg serotonin. The predominant lesion was ischaemic necrosis of tubules of patchy distribution. Parahilar areas were usually spared and a narrow subcapsular strip was less severely affected than deeper parts. The early tubular lesions appeared to be an accelerated form of the lesion of complete renal ischaemia. The necrotic tubules were soon relined by epithelium from surviving segments and became dilated. This phase of dilatation corresponded approximatly with the period of diuresis following serotonin injection and was followed by collapse and atrophy of tubules. Possible mechanisms concerned in the sequential appearance of tubular dilatation and collapse were discussed. Many collapsed tubules eventually atrophied and were associated with basement membrane thickening and round cell infiltration. Reflux of necrotic proximal tubule cytoplasm into glomerular capsular spaces occurred in the early stages of the lesion. This lesion is not specific for serotonin nephropathy and can be produced by allowing normal rat kidney to autolyse.

Pregnant Rats Treated With a Serotonin Precursor Have Reduced Fetal Weight and Lower Plasma Volume and Kallikrein Levels

“…The fact that serotonin may induce renal cortical necrosis in the rat was described long time ago, 19 and in 1955 Page postulated serotonin as the vasoconstrictor substance responsible for renal cortical necrosis as seen in pregnant patients after placental abruption as reviewed in Reference 20. Other authors have characterized the progress of serotonin-induced renal lesions that include an initial ischemic tubular necrosis, followed by dilatation and atrophy of the tubules, 21 which are alterations similar to our findings. In the rat kidney, vasoconstriction-inducing 5-HT 2 receptors have been described in arcuate and interlobar arteries, whereas 5HT 1 receptors present in afferent and efferent arterioles and in the glomeruli cause vasodilation.…”

Functional Acute Renal Failure in a Patient with Carcinoid Syndrome

“…Renal function tests in basal conditions revealed a normal glomerular filtration rate and a normal filtra tion fraction, but a relatively high renal vascular resist ance. This increased renal vascular resistance can be attributed to the vasoconstrictor effect of serotonin on the afferent arteriole of the glomerulus, as is known from animal experiments [Abboud et al, 1983;Erspamer, 1954], in which even ischemic lesions have been elicited [Murray, 1979]. It has to be mentioned that the urinary 5-OH-indolacetic acid levels were comparable in basal and flushing conditions.…”

Effects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chinese-herb nephropathy

“…Rats given a single intraperitoneal injection of 40 mg/kg serotonin rapidly developed wedge-shaped areas of ischaemic tubular necrosis and degeneration, as well as interstitial lymphocytic infiltration. After six months, the areas of damage were characterised by cortical scars consisting of atrophic tubules and disappearance of glomeruli, without significant interstitial fibrosis (Murray 1979). More recently, Colson and colleagues showed in rats that weekly intraperitoneal injection of serotonin at 20, 30 or 40 mg/kg body weight for 3 consecutive weeks induced local vasoconstriction of the arcuate and interlobar arteries, leading to ischaemic lesions with tubular necrosis and tubular dilatation, interstitial hypercellularity and fibrosis (Colson et al 1999).…”