A Comparative Study of the Distributions of Renin and Angiotensinogen Messenger Ribonucleic Acids in Rat and Mouse Tissues*

Abstract

Previous studies have reported the presence of renin mRNAs in several mouse tissues and angiotensinogen mRNAs in various rat tissues. Clarification as to whether renin and angiotensinogen mRNAs are coexpressed in the same tissues of the same animal species is important for understanding the biology of the tissue renin-angiotensin system. We employed mouse renin cDNA and rat angiotensinogen cDNA to compare tissue distributions of renin and angiotensinogen in RNAs of the rat and mouse. Both cDNA probes readily cross-hybridize with the corresponding mRNA of the other species. Our results demonstrate several patterns of distribution. Renin and angiotensinogen mRNAs are readily detected in kidney and adrenals of both species. In brain and heart, angiotensinogen mRNAs are present in concentrations that far exceed renin mRNA levels in these organs in both species. In mouse and rat livers, angiotensinogen, but not renin, mRNA is demonstrated. In rat testis, only renin mRNA can be detected, whereas in mouse testes both renin and angiotensinogen mRNA are present. In CD-1 male mouse submandibular gland, renin mRNA exists in high concentrations, whereas angiotensinogen mRNA is present in low levels. In contrast, neither renin nor angiotensinogen mRNA could be detected in rat salivary gland. In summary, our study demonstrates the widespread codistribution of renin and angiotensinogen mRNAs in many tissues of both species, allowing for the possibility of local angiotensin production. However, tissue and species differences in these gene expressions also exist. Understanding differential tissue expressions of these genes will provide additional important insight into the biology of the renin-angiotensin system.

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

“…The presence of a local as distinct from a systemic renin-angiotensin system (RAS) has been established in several organ systems [52,53] including the eye where the presence of all components of the RAS including its receptors have been identified [8, 54±56]. The beneficial effect of ACE inhibition on retinopathy in patients with diabetes was recently shown in the EUCLID study where treatment with lisinopril was associated with a statistically significant reduction in the progression of retinopathy [11] confirming the results of several earlier trials with ACE inhibitors in which the benefits achieved approached but did not reach pre-defined levels of statistical significance [60±62].…”

Local renin-angiotensin system in human adrenals and aldosteronomas.

“…Homogenates were centrifuged for 30 minutes at 14,000g, and supernatants were used for renin assay. The extraction procedure allowed the recovery of 86.4±5.8% (mean±SEM, n=4) of 50 pg and 88.2±6.1% of 100 pg (n=4) of Medical Research Council human renin standard (1 pg=1.6xlO" 6 Goldblatt Units, World Health Organization International Reference Preparation 68/ 356) added to adrenal samples.…”

“…5 Many studies reported the presence of some RAS components in the adrenals of various animal species. Renin messenger RNA (mRNA), as well as renin immunoreactivity and activity, has been demonstrated in mouse and rat adrenals 6 and localized in the zona glomerulosa cells. 78 Angiotensinogen mRNA has been detected in mouse and rat adrenals, 6 even though it appears to be mainly expressed in periadrenal fibroblast-like cells and brown adipocytes.…”

“…Renin messenger RNA (mRNA), as well as renin immunoreactivity and activity, has been demonstrated in mouse and rat adrenals 6 and localized in the zona glomerulosa cells. 78 Angiotensinogen mRNA has been detected in mouse and rat adrenals, 6 even though it appears to be mainly expressed in periadrenal fibroblast-like cells and brown adipocytes. 9 The presence of angiotensin converting enzyme (ACE) in rat adrenals has been suggested by binding studies with labeled ACE inhibitors.…”

A Case of Renin Producing Leiomyosarcoma Originating in the Lung.

“…Most of these tumors develop in the kidney as hemangiopericytoma (juxtaglomerular cell tumor), nephroblastoma (Wilms' tumor), renal clear cell carcinoma (Grawitz's tumor) and renal hamartoma. Since the production of renin has been identified in the brain, blood vessel walls, adrenal, ovary and testis in addition to the kidney [2][3][4], extra-renal renin secreting tumors have been reported in tumors which developed in the genital organs [5][6][7], the hemangiopericytes of the eye [8] and the adrenal [9]. However, extra-renal renin secreting tumors are very uncommon and only 20 cases have been described so far in the literature.…”