Postnatal early overnutrition dysregulates the intrarenal renin–angiotensin system and extracellular matrix-linked molecules in juvenile male rats

The occurrence of a functional intracellular renin-angiotensin system (RAS) has emerged as a new paradigm. Recently, we and others demonstrated intracellular synthesis of ANG II in cardiac myocytes and vascular smooth muscle cells that was dramatically stimulated in high glucose conditions. Cardiac fibroblasts significantly contribute to diabetes-induced diastolic dysfunction. The objective of the present study was to determine the existence of the intracellular RAS in cardiac fibroblasts and its role in extracellular matrix deposition. Neonatal rat ventricular fibroblasts were serum starved and exposed to isoproterenol or high glucose in the absence or presence of candesartan, which was used to prevent receptor-mediated uptake of ANG II. Under these conditions, an increase in ANG II levels in the cell lysate represented intracellular synthesis. Both isoproterenol and high glucose significantly increased intracellular ANG II levels. Confocal microscopy revealed perinuclear and nuclear distribution of intracellular ANG II. Consistent with intracellular synthesis, Western analysis showed increased intracellular levels of renin following stimulation with isoproterenol and high glucose. ANG II synthesis was catalyzed by renin and angiotensin-converting enzyme (ACE), but not chymase, as determined using specific inhibitors. High glucose resulted in increased transforming growth factor-β and collagen-1 synthesis by cardiac fibroblasts that was partially inhibited by candesartan but completely prevented by renin and ACE inhibitors. In conclusion, cardiac fibroblasts contain a functional intracellular RAS that participates in extracellular matrix formation in high glucose conditions, an observation that may be helpful in developing an appropriate therapeutic strategy in diabetic conditions.

Download Full-text

The effect of angiotensin II on plasminogen activator(PA) system in mesangial cells: the role of renin-angiotensin system in the regulation of glomerular extracellular matrix metabolism.

Nihon Shoni Jinzobyo Gakkai Zasshi ◽

10.3165/jjpn.10.1 ◽

1997 ◽

Vol 10 (1) ◽

pp. 1-5

Author(s):

Shoji Kagami ◽

Takashi Kuhara ◽

Koji Yasutomo ◽

Kaname Okada ◽

Shuji Kondo ◽

...

Keyword(s):

Extracellular Matrix ◽

Angiotensin Ii ◽

Plasminogen Activator ◽

Mesangial Cells ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Matrix Metabolism ◽

Glomerular Extracellular Matrix

Download Full-text

Role of Renin Angiotensin System in Isoproterenol-Induced Myocardial Infarction in Male Rats

Bulletin of Egyptian Society for Physiological Sciences ◽

10.21608/besps.2020.39860.1073 ◽

2021 ◽

Vol 0 (0) ◽

pp. 316-330

Author(s):

lashin saad ◽

ahmed shata ◽

manal hamouda ◽

Mona Elhadidy

Keyword(s):

Myocardial Infarction ◽

Renin Angiotensin System ◽

Male Rats ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

The Type of Fat in the Diet Influences Regulatory Aminopeptidases of the Renin-Angiotensin System and Stress in the Hypothalamic-Pituitary-Adrenal Axis in Adult Wistar Rats

Nutrients ◽

10.3390/nu13113939 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3939

Author(s):

Germán Domínguez-Vías ◽

Ana Belén Segarra ◽

Manuel Ramírez-Sánchez ◽

Isabel Prieto

Keyword(s):

Adrenal Gland ◽

Eating Behavior ◽

Virgin Olive Oil ◽

Renin Angiotensin System ◽

Male Rats ◽

Standard Diet ◽

Angiotensin System ◽

Hypothalamic Pituitary Adrenal ◽

Renin Angiotensin ◽

Dpp Iv

(1) Background: Prolonged feeding with a high-fat diet (HFD) acts as a stressor by activating the functions of the hypothalamic-pituitary-adrenal gland (HPA) stress axis, accompanied of hypertension by inducing the renin-angiotensin-aldosterone system. Angiotensinases enzymes are regulatory aminopeptidases of angiotensin metabolism, which together with the dipeptidyl peptidase IV (DPP-IV), pyroglutamyl- and tyrosyl-aminopeptidase (pGluAP, TyrAP), participate in cognitive, stress, metabolic and cardiovascular functions. These functions appear to be modulated by the type of fat used in the diet. (2) Methods: To analyze a possible coordinated response of aminopeptidases, their activities were simultaneously determined in the hypothalamus, adenohypophysis and adrenal gland of adult male rats fed diets enriched with monounsaturated (standard diet (S diet) supplemented with 20% virgin olive oil; VOO diet) or saturated fatty acids (diet S supplemented with 20% butter and 0.1% cholesterol; Bch diet). Aminopeptidase activities were measured by fluorimetry using 2-Naphthylamine as substrates. (3) Results: the hypothalamus did not show differences in any of the experimental diets. In the pituitary, the Bch diet stimulated the renin-angiotensin system (RAS) by increasing certain angiotensinase activities (alanyl-, arginyl- and cystinyl-aminopeptidase) with respect to the S and VOO diets. DPP-IV activity was increased with the Bch diet, and TyrAP activity decrease with the VOO diet, having both a crucial role on stress and eating behavior. In the adrenal gland, both HFDs showed an increase in angiotensinase aspartyl-aminopeptidase. The interrelation of angiotensinases activities in the tissues were depending on the type of diet. In addition, correlations were shown between angiotensinases and aminopeptidases that regulate stress and eating behavior. (4) Conclusions: Taken together, these results support that the source of fat in the diet affects several peptidases activities in the HPA axis, which could be related to alterations in RAS, stress and feeding behavior.

Download Full-text