Tissue from 1 Year Old Male Rhesus Monkey, Macaca mulatta

SIGNALMENT:

Approximately 1 year old, male, Rhesus monkey, Macaca mulatta

HISTORY:

Routine 3 month oral toxicity study in monkeys with an angiotensin II AT1 receptor antagonist. 

GROSS PATHOLOGY:

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

CONTRIBUTOR’S COMMENTS:

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.

REFERENCES:

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. 

 

r15a.jpg

Kidney from a monkey, H&E, 40x

r15b.jpg

Kidney from a monkey, H&E, 60x
 

r15c.jpg

Kidney from a monkey, Bowie’s stain, 60x

r15d.jpg

 Kidney from a monkey, Bowie’s stain, 80x


 

4 Comments
5 Likes

Rhesus glomeruli

August 2, 2018 06:18 PM by Brett Holliday Saladino, DVM, DACVP

I would call it juxtaglomerular hyperplasia.  I have not seen it before, but I would look carefully at the adrenals and the clinical chemistry/electrolytes for abnormalities.

Rhesus glomeruli

August 2, 2018 06:18 PM by Brett Holliday Saladino, DVM, DACVP

The Bowie stain is gorgeous.

Glomerular lesion

August 7, 2018 07:30 AM by Anantharaman Muthuswamy, DVM, MS, PhD, Dipl. ACVP

I may be totally wrong.  It looks like a mesangioproliferative glormerulopathy.  This picture is similar, but less severe, to the one shown in the manuscript on proliferative and non-proliferative lesions of the rat and mouse urinary system, Fig 56.  

Nice, thanks.

November 14, 2018 11:59 AM by Robert Read, DVM, PhD

If this is representative, I think the morphologic diagnosis is spot on. Wonder which cell type(s) ?

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