| 1. |
- Pasanen, L., et al.
(författare)
-
Age-related changes in the local intestinal renin-angiotensin system in normotensive and spontaneously hypertensive rats
- 2019
-
Ingår i: Journal of Physiology and Pharmacology. - : Polish Physiological Society. - 0867-5910 .- 1899-1505. ; 70:2, s. 199-208
-
Tidskriftsartikel (refereegranskat)abstract
- Local renin-angiotensin systems (RAS) are found in many tissues. The main physiological effects of RAS are driven by the balance between two pathways: the angiotensin-converting enzyme I - angiotensin II receptor type 1 (ACE1-AT1R) axis and the angiotensin-converting enzyme 2 - Mas-receptor (ACE2-MAS) axis. The local intestinal RAS functions both as a paracrine regulator and as a regulator of inflammation. The expression of local RAS is known to change with age in many tissues, but age-related changes in the intestinal RAS have not been studied comprehensively. The present study characterized age-related changes in two main pathways of local RAS in the jejunum and colon of young and adult rats, in normotensive and hypertensive strains. The main finding was that 33-week-old rats exhibit an increased ratio of ACE1/ACE2 activities and protein quantity ratios compared to young rats. As the relationship of ACE1 and ACE2 mediated pathways drives the total physiological effects of RAS, the results indicate that the function of intestinal RAS changes with age. It is possible that age-related increase in ACE1-AT1R axis introduces more pro-inflammatory and fibrogenic conditions in the intestine.
|
|
| 2. |
- Salmenkari, H., et al.
(författare)
-
Orally administered angiotensin-converting enzyme-inhibitors captopril and isoleucine-proline-proline have distinct effects on local renin-angiotensin system and corticosterone synthesis in dextran sulfate sodium-induced colitis in mice
- 2017
-
Ingår i: Journal of Physiology and Pharmacology. - : Polish Physiological Society. - 0867-5910 .- 1899-1505. ; 68:3, s. 355-362
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of angiotensin-converting enzyme (ACE) inhibition by an antihypertensive drug, captopril, and milk casein-derived ACE-inhibiting bioactive tripeptide isoleucine-proline-proline (Ile-Pro-Pro), on local renin-angiotensin system (RAS) and glucocorticoid production in the intestine were studied in the dextran sodium sulfate induced colitis in mice. Mice received water or 3% dextran sodium sulfate with or without either 15.7 mg/l captopril or 833 mg/l Ile-Pro-Pro for 7 days. Captopril and Ile-Pro-Pro were found to have distinct effects on local renin-angiotensin system and mRNA expression of glucocorticoid synthesis components in colon in vitro. Captopril reduced intestinal mRNA expression of angiotensin-converting enzyme, angiotensinogen and Cyp11b1, whereas Ile-Pro-Pro reduced angiotensin-converting enzyme protein shedding from colon. Neither captopril nor Ile-Pro-Pro changed the expression of glucocorticoid-synthesis driving transcription factor Lrh-1 expression or intestinal glucocorticoid production. Contrary to previous studies, captopril did not alleviate DSS-induced colitis. Furthermore, Ile-Pro-Pro was mildly pro-inflammatory as exhibited by increased pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) levels in colon. The nutritional component Ile-Pro-Pro had different effect on intestinal RAS and glucocorticoid (GC) synthesis pathway than ACE inhibitor captopril, which suggests that the bioactivity of Ile-Pro-Pro is not limited to inhibition of ACE.
|
|
