METHODOLOGY: A single center, prospective, single-blind randomized trial was conducted to estimate the survival of post-dialysis euvolemic hypertensive patients when treated with lorsartan 50 mg every other day. Post-dialysis euvolemic assessment was done by a body composition monitor. Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm, and the follow-up duration was twelve months. The primary end point was achieving targeted blood pressure (BP) of <140/90 mm Hg and maintaining for 4 weeks, whereas secondary end point was all cause of mortality. Pre-, intra-, and post-dialysis session BP measurements were recorded, and survival trends were analyzed using Kaplan-Meier analysis.
RESULTS: Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard (n = 44) and intervention arms (n = 44), and 36 (81.8%) patients in each arm completed a follow-up of 12 months. A total of eight patients passed away during the 12-month follow-up period (6 deaths among standard arm and 2 in intervention arm). However, the probability of survival between both arms was not significant (p = 0.13). Cox regression analysis revealed that chances of survival were higher among the patients in the intervention (OR 3.17) arm than the standard arm (OR 0.31); however, the survival was found not statistically significant.
CONCLUSION: There was no statistical significant difference in 1 year survival of post-dialysis euvolemic hypertensive patients when treated with losartan 50 mg.
Materials and Methods: A total of 149 and 150 patients were randomized to intervention and usual care (control) groups, respectively. A 12-month task-shifting (nurse-driven) HBFC intervention was administered to intervention group. The mid-term impact of intervention on HRQoL was assessed after 6 months intervention. Data were analyzed with intention-to-treat principle. Treatment effects were measured with the t-tests, analysis of covariance, and multivariate analysis of covariance analysis. Significant levels were set at P < 0.05 and 95% confidence interval.
Results: The between-group treatment effect was not statistically significant (P > 0.05), whereas the within-group treatment effects were statistically significant for both the intervention and control arms (P < 0.05) at 6 months. After controlling for age and baseline HRQoL, the intervention group had an improved physical component of HRQoL than the control group. The intervention group also had statistically significant improvement in blood pressure control, medication adherence, and symptom counts (P < 0.05).
Conclusion: The HBFC intervention for hypertensive patients impacted positively on physical component of HRQoL after controlling for baseline HRQoL and age of the patients at 6 months post-intervention.
MATERIALS AND METHODS: The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.
KEY FINDINGS: The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.
SIGNIFICANCE: The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.
METHODS: Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract (ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP (HFZOP) with incubation of different antagonists such as Nω-nitro-l-arginine methyl ester (L-NAME, 10 µmol/L), indomethacin (10 µmol/L), methylene blue (10 µmol/L), atropine (1 µmol/L), glibenclamide (10 µmol/L), prazosin (0.01 µmol/L), and propranolol (1 µmol/L).
RESULTS: During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium.
CONCLUSION: This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+ release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.