[Morphological characteristic of renal injury in hypertensive rat strain transgenic for the mouse Ren-2 renin gene (TGR [mRen2] 27].

Abstract

The hypertensive rat strain transgenic for the mouse Ren-2 renin gene (TGR) strain name TGR [mRen 2] 27 is a valuable monogenic model of renin-dependent and thus angiotensin II dependent hypertension. It carries a salt -sensitive component. Homozygous animals exhibit clinically and morphologically typical sings of fulminant hypertension. Glomerular changes in accelerated (malignant) hypertension are acute or chronic. The acute changes have focal character; the most obvious change is segmental fibrinoid necrosis. Fibrinoid necrosis may extend from a similar lesion in the afferent arteriole and may be associated with crescent. Chronic changes are of two different types. The first is similar to that seen in benign hypertension, in that there is collapse of the capillary tuft with wrinkling of the glomerular basement membrane accompanied by collagenization of Bowmann's space. In the second type, glomeruli are also collapsed but seem almost acellular. Male heterozygous TGR are more suitable for experiments because their hypertension is lower and this model is much more similar to clinical situation. Morphologically prominent hyalinosis and segmental sclerotisation of capillary tuft of some glomeruli is present. These features correspond to secondary form of focal segmental glomerulosclerosis (FSGS). High salt diet in heterozygous animals induces a transition from benign to malignant phase of hypertension. In such case ischemic changes are superimposed on the pre-existing renal parenchymal disease (secondary FSGS). Selective blockade of endothelin receptors ET(A) is superior to non-selective ET(A)/ET(B) blockade in attenuating of hypertension and also morphology. ET receptor blockade in homozygous and heterozygous TGR has similar effect on morphological structure of renal parenchyma applied in rats with established hypertension as in young animals. Podocyte injury is crucial also in experimental hypertensive glomerulopathy. Podocytes showed degenerative changes and thickening of glomerular basement membrane was also present. Degree of morphological podocyte injury rather than hypertension correlated with mortality in homozygous TGR.