Approximately 1 year old, male, Rhesus monkey, Macaca mulatta
Routine 3 month oral toxicity study in monkeys with an angiotensin II AT1 receptor antagonist.
LABORATORY RESULTS: (clinical pathology, microbiology, etc…)
MORPHOLOGIC DIAGNOSI(E)S AND ETIOLOGY:
Marked diffuse chronic juxtaglomerular cell hypertrophy and hyperplasia
Etiology: chronic administration of angiotensin II receptor antagonist
The juxtaglomerular (JG) cells are present in the afferent arteriole entering the glomerulus. This arteriole is part of the JG apparatus, which also includes the efferent arteriole, macula densa, and Goormaghtigh’s cells. The JG cells function in the synthesis and release of renin in response to low blood pressure at the glomerulus. Renin functions to activate/cleave angiotensinogen to form angiotensin I. Angiotensin I is then cleaved by angiotensin converting enzyme to angiotensin II, which then acts as a vasoconstrictor to increase blood pressure, and increase Na+ retention by stimulating aldosterone (Kem and Brown, 1990).
JG cell hypertrophy and hyperplasia are known to be induced by both ACE inhibitors and AII receptor antagonists. For ACE inhibitors, it is thought that the plasma concentration of AII is decreased thus preventing the negative feedback of renin release. AII receptor antagonists block the ATI receptor, thereby inhibiting renin release. The result is hypertrophy with an increased number of renin granules in JG cells as well as hyperplasia of these cells (Owen et al., 1994).
This case demonstrates the results of the exaggerated pharmacological effect of angiotensin II receptor antagonists. The special stains (Bowie stain) demonstrates the increased granularity in the hypertrophied cells that corresponds to increased renin content.
Kem DC, Brown RD (1990). Renin from beginning to end. New England Journal of Medicine 323:1136-1137.
Owen RA, Molon-Noblot S, Hubert MF, Siegl PKS, Eydelloth RS, Keenan KP (1994). Juxtaglomerular cell hypertrophy and hyperplasia induced in rhesus monkeys by angiotensin II receptor antagonists. Laboratory Investigation 71:543-551.
Kidney from a monkey, H&E, 40x
Kidney from a monkey, H&E, 60x
Kidney from a monkey, Bowie’s stain, 60x
Kidney from a monkey, Bowie’s stain, 80x