MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K + at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α 1 and 5-HT 2 receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo . Further evidence showed MT bound to and interacted with these receptor subtypes including α 1A , α 1B , α 1D , 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention.
A highly sensitive electrochemical sensor was developed for the detection of the novel antihypertensive drug lercanidipine (LCP). Using zirconium oxychloride (ZrOCl 2 ·8H 2 O) and graphene oxide (GO) as raw materials, polydiallyldimethylammonium chloride (PDDA) as the eco-friendly reducing agent, nano-zirconium dioxide/reduced GO/PDDA (ZrO 2 –rGO–PDDA) composite was prepared by hydrothermal synthesis with doped cerium chloride. Transmission electron microscopy, Fourier transform infrared spectrum, and electrochemical impedance spectroscopy were employed to characterize ZrO 2 –rGO–PDDA composite. The electrochemical behavior of LCP at ZrO 2 –rGO–PDDA modified glassy carbon electrode (ZrO 2 –rGO–PDDA/GCE) was studied by voltammetry. Under optimized measurement conditions, the linear plot between the peak current of LCP and its concentration was found within the range of 4.00 × 10 –7 –1.58 × 10 –4 mol/L, with a detection limit of 8.26 × 10 –8 mol/L. This new sensor was employed successfully to determine the content of LCP drug on the market. The spiked recovery experiments showed that the recoveries of LCP ranged from 97.78 to 101.04%. The developed sensor exhibits high sensitivity and accuracy for the determination of LCP.
危险品化学品经营许可证（带存储）