Effect of antihypertensive agents on stellate cells during liver regeneration in rats

Abstract

-Background -Although most studies have focused on the hepatocytes, all the hepatic cells participate in the regenerative process, among them the stellate cells. The stellate cells are mesenchymal cells involved in local neurotransmission and paracrine regulation of several liver functions. Acute hepatic tissue loss promotes the proliferation and activation of stellate cells from a quiescent state to myofibroblast-like cells. Aim -Investigate the effects of antihypertensive agents on the stellate cell population during the liver regenerative phenomenon in rats. Methods -Adult male Wistar rats received lisinopril, losartan, bradykinin, or saline solution in a proportional volume, intraperitoneally, before and after 70% partial hepatectomy. Animals from the experimental and saline groups were sacrificed at 36 hours after partial hepatectomy. The alpha-smooth muscle actin labelled stellate cells population was counted in the periportal and pericentral zones of the liver specimen. Results -The labelled stellate cells were more numerous in the control group both in the periportal and pericentral zones at 36 hours after partial hepatectomy than at the other times. The population of stellate cells was significantly lower in the losartan group and higher in the bradykinin and lisinopril groups than in the control group. Conclusions -These results suggest that losartan can inhibit and bradykinin and lisinopril can stimulate the stellate cell population during liver regeneration in rats. These cells synthesize several substances to stimulate liver regeneration.

Blockade of the renin–angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver

“…Pharmacological blockade of various components of the RAS inhibit CRCLM tumor growth, proliferation and angiogenesis (12,13,17,19,(25)(26)(27)(28). RAS blockade has also been found to significantly enhance liver regeneration in animal models (19)(20)(21)(22)29). While the effects of the ACE inhibitor, captopril, on CRCLM and on the RAS expression in tumors have been documented (12), it is unknown whether these beneficial outcomes can be achieved in the same patient.…”

Liver growth prediction in ALPPS – A multicenter analysis from the international ALPPS registry

“…It is well known that the use of antihypertensive treatment is related to NASH. In human, there is no evidence of the relationship of these drugs with liver regeneration, but in animals Ramalho et al describe that the losartan treatment diminished the activated stellate cell population, which is also known to participate in the liver fibrosis process 34 . On the other hand, Ambreen et al concluded that ACE inhibitor, lisinopril, did not produce major histo‐morphological alterations in regenerating fibrotic livers 48 h following partial hepatectomy in a rat model with the exception of non‐significant mitosis inhibition and increased hepatocyte binucleation 35 .…”

Effect of angiotensin-converting enzyme inhibitor, lisinopril on morphological and biochemical aspects of fibrotic liver regeneration

“…It could be said that lisinopril treatment can reduce fibrosis in normal rats significantly, however, in regenerating fibrotic livers, it cannot produce a significant effect. These drugs are reported to activate stellate cells in regenerating livers,[41] which are the major fibrogenic cells of liver. [42]…”