This study aims to investigate the effects of renin inhibitor aliskiren on kidney injury in human angiotensinogen-renin (AGT-REN) double transgenic hypertensive (dTH) mice and explore its possible mechanism. The dTH mice were divided into hypertension group (HT group) and aliskiren intervention group (HT+Aliskiren group), while wild-type C57BL/6 mice were served as the control group (WT group). Blood pressure data of mice in HT+Aliskiren group were collected after 28 d of subcutaneous penetration of aliskiren (20 mg/kg), and the damage of renal tissue structure and collagen deposition were observed by HE, Masson and PAS staining. The ultrastructure of kidney was observed by transmission electron microscope. Coomassie bright blue staining and biochemical analyzer were used to detect renal function injury. The expression of renin-angiotensin system (RAS) was determined by ELISA and immunohistochemistry. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney were determined by chemiluminescence method. The content of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47^phox, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine (3-NT), NADPH oxidase 2 (NOX2) and NADPH oxidase 4 (NOX4) were detected by Western blot analysis. The results showed that compared with WT group, the blood pressure of mice in HT group was significantly increased. The renal tissue structure in HT group showed glomerular sclerosis, severe interstitial tubular injury, and increased collagen deposition. In addition, 24 h urinary protein, serum creatinine and urea levels increased. Serum and renal tissue levels of angiotensin II (Ang II) were increased, serum angiotensin-(1-7) [Ang-(1-7)] expression was decreased, and renal Ang-(1-7) expression was elevated. The expressions of ACE, Ang II type 1 receptor (AT₁R) and MasR in renal tissue were increased, while the expression of ACE2 was decreased. MDA content increased, SOD content decreased, and the expressions of p47^phox, iNOS, 3-NT, NOX2 and NOX4 were increased. However, aliskiren reduced blood pressure in dTH mice, improved renal structure and renal function, reduced Ang II and Ang-(1-7) levels in serum and renal tissue, reduced the expression of ACE and AT₁R in renal tissue, increased the expression of ACE2 and MasR in renal tissue, and decreased the above levels of oxidative stress indexes in dTH mice. These results suggest that aliskiren may play a protective role in hypertensive renal injury by regulating the balance between ACE-Ang II-AT₁R and ACE2-Ang-(1-7)-MasR axes and inhibiting oxidative stress.
Animals ; Fumarates/therapeutic use* ; Mice ; Renin/antagonists & inhibitors* ; Amides/therapeutic use* ; Mice, Inbred C57BL ; Hypertension/physiopathology* ; Mice, Transgenic ; Kidney/pathology* ; Angiotensinogen/genetics* ; Renin-Angiotensin System/drug effects* ; NADPH Oxidases/metabolism* ; Male ; Antihypertensive Agents/pharmacology* ; Humans ; Superoxide Dismutase/metabolism* ; NADPH Oxidase 4

Objective: To evaluate the clinical effect of vonoprazan fumarate on laryngopharyngeal reflux disease (LPRD). Methods: The clinical data of 89 patients from June 2020 to January 2022, including 45 males and 44 females, aged 18-77 (45.54±13.53) years old, were retrospectively analyzed. All the patients were diagnosed as suspected LPRD according to reflux symptom index (RSI) and reflux finding score (RFS). Patients of the Vonoprazan Fumarate group were prescribed Vonoprazan Fumarate orally (20 mg, qd) for 8 weeks.Patients of the Esomeprazole group were prescribed Esomeprazole orally (20 mg, bid) for 8 weeks. RSI and RFS of all the patients before and after treatment were compared. SPSS 18.0 was used for statistics analysis. Results: Before treatment, gender, age, RSI and RFS of the two groups had no obvious differences. After treatment, RSI and RFS in both groups were alleviated significantly. In the vonorazan fumarate group, the RSI before treatment was 12.62±7.18, and after treatment was 4.74±3.87(t=6.91, P<0.001), the RFS was 10.78±2.29 before treatment and 8.24±2.45 after treatment (t=7.06, P<0.001). While in the esomeprazole group, the RSI was 13.27±6.95 before treatment and 6.02±4.28 after treatment (t=7.50, P<0.001), the RFS was 10.59±3.14 before treatment and 8.14±3.30 after treatment (t=5.41, P<0.001). There was no significant difference in the effective rate between the two groups (86.7% in the vonoprazan fumarate group and 77.3% in the esomeprazole group, χ²=1.443, P=0.486). Conclusion: Vonoprazan fumarate could effectively alleviate the symptoms and signs of LPRD patients. The effect of vonoprazan fumarate on LPRD is not inferior to Esomeprazole. It can be used as a supplement to PPI.
Humans ; Male ; Female ; Adult ; Middle Aged ; Laryngopharyngeal Reflux/diagnosis* ; Esomeprazole/therapeutic use* ; Retrospective Studies ; Fumarates/therapeutic use*

BACKGROUNDAliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated.

METHODSMale Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups: angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, β adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed.

RESULTSThe plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats.

CONCLUSIONSAliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.

Amides ; pharmacology ; therapeutic use ; Animals ; Fumarates ; pharmacology ; therapeutic use ; Male ; Myocardial Infarction ; blood ; drug therapy ; Norepinephrine ; blood ; Rats ; Rats, Sprague-Dawley ; Renin ; antagonists & inhibitors ; Sympathetic Nervous System ; drug effects ; Tachycardia, Ventricular ; prevention & control

BACKGROUNDAliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients.

METHODSFollowing a two week placebo run-in period, patients with a mean sitting diastolic blood pressure (ms-DBP) ≥ 95 and < 110 mmHg (1 mmHg = 0.133 kPa), and a mean sitting systolic blood pressure (ms-SBP) < 180 mmHg were randomly allocated to treatment with aliskiren (150 mg/d, n = 20) or ramipril (5 mg/d, n = 20) for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity (ba-PWV) were measured before and after eight weeks of treatment.

RESULTSEight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensive effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups (P = 0.892). The ba-PWV was significantly reduced in both the aliskiren group (1535 (1405 - 1666) vs. 1464 (1360 - 1506) cm/s) (P < 0.01) and the ramipril group (1544 (1433 - 1673) vs. 1447 (1327 - 1549) cm/s) (P < 0.01). No statistically significant difference was found in the decline of ba-PWV between the two groups (P = 0.766).

CONCLUSIONSThe current study revealed that aliskiren (150 mg/d) could ameliorate arterial stiffness and its effect was similar to ramipril (5 mg/d) in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.

Adult ; Amides ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Female ; Fumarates ; therapeutic use ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged ; Ramipril ; therapeutic use ; Vascular Stiffness ; drug effects

Amides ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Female ; Fumarates ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Male ; Ramipril ; therapeutic use ; Vascular Stiffness ; drug effects