Hypotensive activity of Campomanesia xanthocarpa leaf extract: beyond angiotensin II type 1 receptor blockage.

The ability of Campomanesia xanthocarpa leaf extract (CXLE) to alter blood pressure and heart rate was evaluated in anesthetized rats. The CXLE-induced hypotension was evaluated before and after losartan, methylatropine, L-N(ω)-nitro-L-arginine methyl ester (L-NAME), hexamethonium, indomethacin, glibenclamide, or nifedipine administration. The constituents of CXLE were identified by LC-DAD-MS. CXLE decreased blood pressure in a dose-dependent manner; only the highest dose decreased heart rate. The hypotension induced by CXLE was sensitive only to losartan, nifedipine, and glibenclamide. L-NAME decreased the time to recover 50% of the hypotensive effect of CXLE without altering its magnitude. Flavan-3-ols, proanthocyanidins (dimers and trimers), and glycosylated flavonols were identified from CXLE. The chemical constituents of CXLE seem to induce not only angiotensin II type 1 receptor blockage, but also ATP-sensitive potassium channels activation and L-type voltage-dependent Ca2+ channels inactivation. Nitric oxide is involved in the maintenance of the hypotensive effect of CXLE.

AC biosusceptometry and magnetic nanoparticles to assess doxorubicin-induced kidney injury in rats.

Aim: This paper aims to investigate a doxorubicin (DOX) chronic kidney disease rat model using magnetic nanoparticles (MNPs) associated with the alternate current biosusceptometry (ACB) to analyze its different perfusion profiles in both healthy and DOX-injured kidneys. Materials & methods: We used the ACB to detect the MNP kidney perfusion in vivo. Furthermore, we performed biochemical and histological analyses, which sustained results obtained from the ACB system. We also studied the MNP biodistribution. Results: We found that DOX kidney injury alters the MNPs' kidney perfusion. These changes became more intense as the disease progressed. Moreover, DOX has an important effect on MNP biodistribution as the disease evolved. Conclusion: This study provides new applications of MNPs in nephrology, instrumentation, pharmacology, physiology and nanomedicine.

Hypotensive effect of Eugenia dysenterica leaf extract is primarily related to its vascular action: The possible underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia dysenterica (ED) leaves are used in Brazil to treat cardiac diseases; however, there are no scientific data describing the effects of this species on cardiac activity. AIM OF THE STUDY: To investigate the effect of ED aqueous leaf extract (EDLE) on hear rate (HR) and mean arterial pressure (MAP) of anaesthetised rats and its underlying mechanism of action. MATERIAL AND METHODS: EDLE was analysed, and its proanthocyanidin composition was determined. After performing dose-effect curves for EDLE on HR and MAP, EDLE-induced hypotension was evaluated before and after atropine (AT), L-N(ω)-nitro-L-arginine methyl ester (L-NAME), hexamethonium (HXT), indomethacin (IND), carbenoxolone (CBX), or nifedipine (NFD) administration. The effect of proanthocyanidin-depleted extract (EDLE/P-) was also determined and compared to that of the EDLE with proanthocyanidins. RESULTS: EDLE decreased the MAP in a dose-dependent manner; HR was decreased only with the highest and most toxic dose. Only CBX and NFD decreased EDLE-induced hypotension. Five polymeric series of proanthocyanidins were identified, which were mainly constituted by procyanidin and prodelphinidin units with B-type linkage and up to 12 flavan-3-ol units. EDLE/P- induced hypotension did not differ from that induced by EDLE. CONCLUSIONS: The cardiovascular effects of EDLE were primarily related to its vascular action. EDLE-induced hypotensive effect appeared to involve L-type calcium channel blockage as well as myoendothelial gap junction signalling. The higher molecular weight proanthocyanidins from EDLE are unlikely to contribute to its cardiovascular effect.

Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.

BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.