| First Author | Majid DSA | Year | 2021 |
| Journal | Physiol Rep | Volume | 9 |
| Issue | 16 | Pages | e14990 |
| PubMed ID | 34427402 | Mgi Jnum | J:314256 |
| Mgi Id | MGI:6766136 | Doi | 10.14814/phy2.14990 |
| Citation | Majid DSA, et al. (2021) Angiotensin II-induced renal angiotensinogen formation is enhanced in mice lacking tumor necrosis factor-alpha type 1 receptor. Physiol Rep 9(16):e14990 |
| abstractText | In hypertension induced by angiotensin II (AngII) administration with high salt (HS) intake, intrarenal angiotensinogen (AGT) and tumor necrosis factor-alpha (TNF-alpha) levels increase. However, TNF-alpha has been shown to suppress AGT formation in cultured renal proximal tubular cells. We examined the hypothesis that elevated AngII levels during HS intake reduces TNF-alpha receptor type 1 (TNFR1) activity in the kidneys, thus facilitating increased intrarenal AGT formation. The responses to HS diet (4% NaCl) with chronic infusion of AngII (25 ng/min) via implanted minipump for 4 weeks were assessed in wild-type (WT) and knockout (KO) mice lacking TNFR1 or TNFR2 receptors. Blood pressure was measured by tail-cuff plethysmography, and 24-h urine samples were collected using metabolic cages prior to start (0 day) and at the end of 2nd and 4th week periods. The urinary excretion rate of AGT (uAGT; marker for intrarenal AGT) was measured using ELISA. HS +AngII treatment for 4 weeks increased mean arterial pressure (MAP) in all strains of mice. However, the increase in MAP in TNFR1KO (77 +/- 2 to 115 +/- 3 mmHg; n = 7) was significantly greater (p < 0.01) than in WT (76 +/- 1 to 102 +/- 2 mmHg; n = 7) or in TNFR2KO (78 +/- 2 to 99 +/- 5 mmHg; n = 6). The increase in uAGT at 4th week was also greater (p < 0.05) in TNFR1KO mice (6 +/- 2 to 167 +/- 75 ng/24 h) than that in WT (6 +/- 3 to 46 +/- 16 ng/24 h) or in TNFR2KO mice (8 +/- 7 to 65 +/- 44 ng/24 h). The results indicate that TNFR1 exerts a protective role by mitigating intrarenal AGT formation induced by elevated AngII and HS intake. |
