Graphical depiction of adrenergic hypertone in cirrhotic rats, treated (G4) or not (G3) with diuretics.

<p>Early (G5) and late (G6) blunting of adrenergic function in cirrhotic rats receiving, respectively, clonidine or guanfacine, along with diuretics.</p

Progressive weight gain of untreated cirrhotic rats (G3, red line) and of cirrhotic rats treated with diuretics (G4, yellow line) or with diuretics plus clonidine (G5, blue line).

<p>Further groups depicted: G1 (healthy controls, black line), G6 (cirrhotic rats treated with diuretics plus oral prodrug of guanfacine, green line). Mean measurements ± SD of three rats studied at a time in each group are depicted.</p

Transient natriuretic effects in G4 (cirrhotic rats treated with furosemide and potassium canrenoate, yellow line) and G5 (cirrhotic rats treated with diuretics plus clonidine, blue line) over CCl₄ weeks 11–12.

<p>Progressive natriuretic effects in G6 (cirrhotic rats treated with diuretics plus oral prodrug of guanfacine, green line). Further groups depicted: G1 (healthy controls, black line), G3 (untreated cirrhotic rats, red line). Mean measurements ± SD of three rats studied at a time in each group are depicted.</p

Hormonal status.

<p>Comparisons between means ± SD of PRA, plasma aldosterone, etc. taken on weeks 11–12 (Group GX_A) vs. weeks 13–14 (Group GX_B) or among different G1–G6 groups. In each group, worsening of clinical parameters <u>underlined</u>, improvements in <b>bold</b> print (weeks 13–14, Group GX_B, vs. weeks 11–12, Group GX_A).</p

Renal function.

<p>Comparisons between means ± SD of FENa, kaliuresis, plasma Na, etc. taken on weeks 11–12 (Group GX_A) vs. weeks 13–14 (Group GX_B) or among different G1–G6 groups. In each group, worsening of clinical parameters <u>underlined</u>, improvements in <b>bold</b> print (weeks 13–14, Group GX_B, vs. weeks 11–12, Group GX_A).</p

Marked increase in PRA (concurrent with development of diuretic-unresponsive ascites) over CCL₄ weeks 13–14 in cirrhotic rats (G3, untreated, red line, and G4, receiving diuretics only, yellow line).

<p>Blunting of renin secretion in G5 (cirrhotic rats treated with diuretics plus clonidine, blue line) and G6 (cirrhotic rats treated with diuretics plus oral prodrug of guanfacine, green line). Further group depicted: G1 (untreated controls, black line). Mean measurements ± SD of three rats studied at a time in each group are depicted.</p

Both human activated, myofibroblast-like, hepatic stellate cells and human hepatoblastoma cells show basal expression of chymase mRNA and a considerable increase in its expression after stimulation with TGF-β1, earlier in HepG2 cells and later in activated stellate cells.

<p>Both human activated, myofibroblast-like, hepatic stellate cells and human hepatoblastoma cells show basal expression of chymase mRNA and a considerable increase in its expression after stimulation with TGF-β1, earlier in HepG2 cells and later in activated stellate cells.</p

Renal distribution of chymase.

<p>Panel A: Indirect immunofluorescence staining of kidney sections from cirrhotic rats (G3 group). Panel B: Immunohistochemical staining for chymase in kidney sections from either control animals (G1) or cirrhotic rats (G3). In the kidney of cirrhotic rats, chymase was found in the wall of cortical arterioles (Panel A), in the wall of proximal convoluted tubules (Panel B, green arrows), in distal convoluted tubules (Panel B, red arrows), and at the vascular pole of the glomerulus (Panel B, black arrow).</p

Chymase immunohistochemical localization in resected samples of normal and cirrhotic human liver.

<p>Original magnification as indicated.</p

Morphological analysis of chronic liver disease progression through αSMA immunohistochemistry.

<p>Administration of chymase inhibitor to healthy rats (G2) did not affect normal liver morphology. 13 weeks of CCl₄ (G3): development of liver cirrhosis (and ascites). The liver of rats receiving both CCl₄ and the chymase inhibitor was characterized by a significant prevention of fibrosis progression towards cirrhosis. This, already appreciable in G4, was maximal in animals treated with 20 mg/kg b.w. of the chymase inhibitor (G5).</p