Released by the juxtaglomerular cells of the kidney, renin catalyzes the first step in the activation pathway of angiotensinogen--a cascade that can result in aldosterone release, vasoconstriction, and increase in blood pressure. Renin cleaves angiotensinogen to form angiotensin I, which is converted to angiotensin II by angiotensin I converting enzyme. Renin occurs in other organs than the kidney, e.g., in the brain, where it is implicated in the regulation of numerous activities.
NCBI Summary:
Renin catalyzes the first step in the activation pathway of angiotensinogen--a cascade that can result in aldosterone release,vasoconstriction, and increase in blood pressure. Renin, an aspartyl protease, cleaves angiotensinogen to form angiotensin I, which is converted to angiotensin II by angiotensin I converting enzyme, an important regulator of blood pressure and electrolyte balance. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause familial hyperproreninemia. [provided by RefSeq, Jul 2008]
Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS. Bayir Y et al. (2016) The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1β, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system./////////////////Safety and efficacy of aliskiren in the treatment of hypertension: a systematic overview. Angeli F et al. (2012) Aliskiren is the first orally active direct renin inhibitor approved for the treatment of hypertension. Aliskiren's inhibitory effect on angiotensin I generation, through renin blockade, is highly specific and long-lasting (24 hours). This feature differentiates aliskiren from traditional antihypertensive drugs. This paper reviews the results of various clinical trials which investigate the safety and efficacy of aliskiren on blood pressure (BP) reduction and clinical end points. Aliskiren is suitable for once-daily administration. Its antihypertensive effect is comparable or superior to that of other antihypertensive agents at recommended doses. The tolerability profile of aliskiren is placebo-like at the licensed doses of 150 and 300 mg. In particular, the discontinuation of therapy due to clinical adverse events occurs similarly among patients treated with either aliskiren or placebo. Aliskiren is not recommended in association with ACE-inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and renal impairment. Pending disclosure of full results, the early termination of the ALTITUDE seems to confirm previous concerns about the safety of the dual pharmacological blockade of the renin-angiotensin system in these patients. Aliskiren is a well-tolerated antihypertensive drug that may help to achieve the recommended targets of BP control.//////////////////
Cellular localization
Secreted
Comment
Changes of plasma renin activity and angiotensin II levels in women with polycystic ovary syndrome]. [Li X et al. (2001) To investigate changes of plasma renin activity(PRA) and plasma angiotensin II (PANG II) in women with polycystic ovary syndrome(PCOS). We chose thirty PCOS women as trial group and thirty normal menstrual women as control. PRA and PANG II levels during follicularphase(FP) of the two groups were measured by radioimmunoassay. PRA and PANG II increased in women with PCOS as compared with the normal FP. The increment of PRA and PANG II in PCOS women of high testosterone levels was correlated with serum luteinizing hormone/follicle-stimulating hormone and testosterone concentration. The elevated PRA and PANG II suggest an enhanced functional activity of ovarian renin angiotensin system in PCOS, and which may play a role in the pathologenesis of PCOS.//////////////////
All components of the renin-angiotensin-system (RAS) are present in the ovary and the ovary secretes components of the RAS into the bloodstream. Furthermore, the ovary itself is responsive to Angiotensin II. Recent studies suggest that the primary role of Ang II in the ovary is to cause atresia in non-ovulatory follicles; however, there is also compelling data to suggest that Ang II facilitates ovulation. However, the overall significance of the RAS for normal reproductive function remains questionable (Speth et al., 1999).
Expression regulated by
LH
Comment
Prorenin and renin production in theca cells are stimulated by luteinizing hormone. Growth factors and cytokines (TNF, FGF, EGF and TGF) can modulate LH-induced prorenin production (Brunswig-Spickenheier et al. (1995) .
Ovarian localization
Granulosa, Luteal cells
Comment
Although the kidney is a major source of prorenin, the selective increase in plasma prorenin at the time of ovulation suggested that one of these sources might be the ovary. Glorioso et al. (1986) reported that the follicular fluid contained high concentrations of prorenin approximately 12 times higher than plasma prorenin. The prorenin from follicular fluid was immunochemically identical to kidney and plasma prorenin. Thus, the ovary is a likely source for the ovulatory peak of plasma prorenin. Glorioso et al. (1988) reported that angiotensin I (Ang I) generating capacity was found in the extracts of the cells retrieved from human hyperstimulated ovarian follicles in women undergoing in-vitro fertilization. More than 90% of this Ang I generating capacity was due to activated prorenin, whereas only less than 10% was due to active renin. This Ang I forming capacity was completely abolished by pre-incubation with polyclonal anti-renin serum. Thus, an intracellular prorenin-renin system can exist in the human ovary than can modulate the ovarian function throughout the menstrual cycle and during pregnancy.Theca cells from bovine ovaries, which had been classified (by biochemical and morphological methods)to be atretic, produce significant higher amounts of prorenin and renin than healthy cells (Mukhopadhyay et al. (1991).
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Itskovitz-Eldor et al. (1997) indicate that the ovary secretes prorenin during early pregnancy and that its secretion is directed preferentially from the luteal cysts into the peritoneal cavity. In light of recent evidence of an effect of prorenin on the vascular system, the presence of a huge reservoir of prorenin in the peritoneal cavity of patients with Ovarian hyperstimulation syndrome (OHSS) suggests a potential role for prorenin in the pathogenesis of this syndrome. Lightman et al. (1987) reported that renin mRNA was detected in gonadotropin-stimulated rat corpus luteum using in situ hybridization histochemistry techniques. No positive signal was detected in theca or granulosa cells. These results indicate ovarian renin gene expression in rat luteal cells, where the renin molecule is probably produced, and support the concept of an intrinsic ovarian renin-angiotensin-system.