Orthosiphon stamineus Benth. (Lambiaceae) is an important traditional plant for the treatment of hypertension. Previous studies have demonstrated that the sinensetin content in O. stamineus is correlated with its vasorelaxant activity. However, there is still very little information regarding the vasorelaxant effect of sinensetin due to a lack of scientific studies. Therefore, the present study was designed to investigate the underlying mechanism of action of sinensetin in vasorelaxation using an in vitro precontraction aortic ring assay. The changes in the tension of the aortic ring preparations were recorded using a force-displacement transducer and the PowerLab system. The mechanisms of the vasorelaxant effect of sinensetin were determined in the presence of antagonists. Sinensetin caused relaxation of the aortic ring precontracted with PE in the presence and absence of the endothelium and with potassium chloride in endothelium-intact aortic rings. In the presence of Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), ODQ (selective soluble guanylate cyclase inhibitor), indomethacin (a nonselective cyclooxygenase inhibitor), tetraethylammonium (nonselective calcium activator K+ channel blocker), 4-aminopyridine (voltage-dependent K+ channel blocker), barium chloride (inwardly rectifying Kir channel blocker), glibenclamide (nonspecific ATP-sensitive K+ channel blocker), atropine (muscarinic receptor blocker), or propranolol (β-adrenergic receptor blocker), the relaxation stimulated by sinensetin was significantly reduced. Sinensetin was also active in reducing Ca2+ release from the sarcoplasmic reticulum (via IP3R) and in blocking calcium channels (VOCC). The present study demonstrates the vasorelaxant effect of sinensetin, which involves the NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors.
Panax notoginseng is the most valuable medicinal plant and has been used clinically for more than two thousand years to treat various diseases, including hypertension. Previous studies claimed that different isolated compounds from P. notoginseng are involved in different pathways for vasodilation. It is strongly believed that these vasodilating compounds might act synergistically in contributing vasodilatory effects via holistic signaling pathways. The present study aims to evaluate the vasodilatory effect and mechanism of action employed by the crude extract of P. notoginseng. The fingerprint of P. notoginseng was developed using tri-step FTIR and HPTLC. The contents of Rg1 and Rb1 in the active extract (PN95) were further quantified via HPTLC. The vasodilatory effect of PN95 was evaluated using an in vitro aortic ring model. The results showed that PN95 contains a high amount of Rg1 and Rb1, 25.9 and 13.6%, respectively. The vasodilatory effect of PN95 was elicited via the NO/sGC/cGMP and β2-adrenergic receptors pathways. Furthermore, PN95 could manage vascular tone by regulating action potentials via potassium and both VOCC and IP3R pathways. The results obtained fulfilled the expected outcome where the PN95 employed more signaling pathways than any of the single active compounds; hence, the holistic therapeutic effect could be achieved and would more easily translate to applications for the treatment of human diseases.
The prevalence of hypertension in Malaysia is alarmingly high. The National Survey in 2006 showed 43% of people aged ≥30 had hypertension and among treated patients, only 26% reached the target blood pressure (BP) of <140/90 mmHg. We evaluated BP control in tertiary institutions in Malaysia and the difference in hypertension control between genders and within specific cardiovascular risk factor groups. This cross-sectional study aimed at determining BP control among hypertensive patients attending three specialist institutions in Malaysia, located in Kuala Lumpur, Kuantan and Kota Bharu. A total of 950 patients with known hypertension for at least 6 months were recruited between January 2007 and July 2008. There were more males (n=548, 57.7%) with a mean age of 60.3±10.5 (±s.d.) years. The mean systolic BP (SBP) and diastolic BP were 138.8±20.3 mmHg and 79.6±11.3 mmHg, respectively. In total, 48.5% of all the patients had good BP control (<140/90 mmHg). Males had better SBP control compared with female (SBP: 135.9±18.7 vs. 142.8±21.7 mmHg, P<0.001). Overall, 54.6% of the patients had ischemic heart disease (IHD), 24.2% had undergone coronary revascularization, 50.1% were diabetic, 68.6% hyperlipidemic, 17.3% smokers and 27.5% had renal impairment. Males and small numbers of antihypertensives used were independently associated with better treatment outcome. In summary, our data reveal a poorer BP control, secondary to higher SBP levels in women. Moreover, the gender difference is more pronounced in patients with concomitant diabetes mellitus, renal impairment and IHD.
Blood pressure has a significant effect on retinal arterioles. There are few data on whether this effect varies by race/ethnicity. We examined the relationship of blood pressure and retinal vascular caliber in a multi-ethnic Asian population. The study is population-based and cross sectional in design. A total of 3749 Chinese, Malay and Indian participants aged > or =24 years residing in Singapore were included in the study. Retinal vascular caliber was measured using a computer program from digital retinal photographs. The associations of retinal vascular caliber with blood pressure and hypertension in each racial/ethnic group were analyzed. The main outcome measures are retinal arteriolar caliber and venular caliber. The results show that retinal arterioles were narrower in persons with uncontrolled/untreated hypertension (140.0 microm) as compared with persons with controlled hypertension (142.1 microm, P=0.0001) and those with no hypertension (146.0 microm, P<0.0001). On controlling for age, gender, body mass index, lipids and smoking, each 10 mm Hg increase in mean arterial blood pressure was associated with a 3.1 microm decrease in arteriolar caliber (P<0.0001), with a similar magnitude seen in all three racial/ethnic groups: 3.1 microm in Chinese, 2.8 microm in Malays and 3.2 microm in Indians (P<0.0001 for all). Each 10 mm Hg increase in mean arterial blood pressure was associated with a 1.8 microm increase in venular caliber (P<0.0001); furthermore, the magnitude of this effect was similar across the three racial/ethnic groups. The effect of blood pressure on the retinal vasculature was similar across three major racial/ethnic groups in Asia.
Although oxidative stress has been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs), there is little information on the levels of primary antioxidant enzymes status (AOEs) in pre-hypertensive SHR. This study therefore determined the activities of primary AOEs and their mRNA levels, levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and total antioxidant status (TAS) in whole kidneys of SHR and age-matched Wistar-Kyoto (WKY) rats aged between 2 and 16 weeks. Compared with age-matched WKY rats, catalase (CAT) activity was significantly higher from the age of 2 weeks (P<0.001) and glutathione peroxide (GPx) activity was lower from the age of 3 weeks (P<0.001) in SHR. CAT mRNA levels were significantly higher in SHR aged 2, 4, 6 and 12 weeks. GPx mRNA levels were significantly lower in SHR at 8 and 12 weeks. Superoxide dismutase activity or its mRNA levels were not different between the two strains. H2O2 levels were significantly lower in SHR from the age of 8 weeks (P<0.01). TAS was significantly higher in SHR from the age of 3 weeks (P<0.05). MDA levels were only significantly higher at 16 weeks of age in the SHR (P<0.05). The data suggest that altered renal CAT and GPx mRNA expression and activity precede the development of hypertension in SHR. The raised CAT activity perhaps contributes to the higher TAS and lower H2O2 levels in SHR. In view of these findings, the precise role of oxidative stress in the pathogenesis of hypertension in SHR needs to be investigated further.
The prevalence of high sodium-related diseases is increasing across the globe. Knowledge plays an important role in disease prevention. The objective of the present study was to examine sociodemographic factors associated with knowledge of high sodium-related diseases. The Malaysian Community Salt Survey (MyCoSS) was used in the present study for secondary analyses. It is a nationwide cross-sectional survey that was conducted in Malaysia. A non-parametric test to evaluate trends and a negative binomial regression were utilised to assess knowledge of high sodium-related diseases. Income, educational level, gender, ethnicity, house locality and hypertension were found to be significantly associated with knowledge of high sodium-related diseases. In particular, higher income earners, well-educated people, women, Malays, urban dwellers and hypertensive adults were more likely to have acquired a lot of knowledge of high sodium-related diseases compared to that acquired by lower income earners, less-educated people, men, individuals of other ethnic groups, rural dwellers and nonhypertensive adults. In conclusion, sociodemographic factors and hypertension play an important role in knowledge acquired about high sodium-related diseases. The findings of the present study could inform a future policy directed towards increasing knowledge about high sodium-related diseases among the population in Malaysia.
We aimed to perform a systematic review and meta-analysis to determine the overall effect of the preadmission/prediagnosis use of calcium channel blockers (CCBs) on the clinical outcomes in hypertensive patients with COVID-19. A systematic literature search with no language restriction was conducted in electronic databases in July 2021 to identify eligible studies. A random-effects model was used to estimate the pooled summary measure for outcomes of interest with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs at 95% confidence intervals (CIs). The meta-analysis revealed a significant reduction in the odds of all-cause mortality with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.65; 95% CI 0.49-0.86) and a significant reduction in the odds of severe illness with preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.61; 95% CI 0.44-0.84), and is associated with adequate evidence to reject the model hypothesis of 'no significant difference' at the current sample size. The potential protective effects offered by CCBs in hypertensive patients with COVID-19 merit large-scale prospective investigations.
High sodium intake was found to be associated with increased blood pressure. Decreasing dietary sodium intake can effectively reduce blood pressure, especially among hypertensive individuals, but the extent of reduction remains debatable. The effectiveness of different sodium reduction strategies on blood pressure reduction was identified in the current review. Randomized controlled trials and clinical trials on dietary sodium intake and blood pressure published from 23 March 2008 to 23 March 2021 were collected from the PubMed database. Twenty-six studies were included and divided into four subgroups based on the types of interventions identified. Subgroups included a low-sodium diet (1) in a group with or without added sodium, (2) through food substitutes, (3) through health education and behavior change, and (4) through salt substitutes. Reduction of dietary sodium intake resulted in a mean difference of 4.51 mmHg (95% CI: 3.35-5.67) in systolic blood pressure and 2.42 mmHg (95% CI: 1.61-3.23) in diastolic blood pressure. The effectiveness of these strategies was approximated from the difference in 24-h urinary sodium excretion between the intervention and control groups, which was 53.74 mmol/day (95% CI: 31.95-75.53). When analyzed, the low-sodium diet without added sodium showed the greatest significant differences in blood pressure (7.58/4.01 mmHg) and 24-h urinary sodium excretion (101.49 mmol/day), whereas the low-sodium diet through food substitutes yielded the lowest significant differences in blood pressure (2.26/0.81 mmHg) and 24-h urinary sodium excretion (25.78 mmol/day). Thus, reducing sodium intake can be an effective strategy for the prevention and treatment of hypertension.
Uncontrolled hypertension is a significant problem in many parts of Asia. Effective management is essential to reduce the burden of hypertension. Home blood pressure monitoring (HBPM) is a promising tool that can aid in the diagnosis and management of hypertension. Experts from 11 countries/regions in Asia conceptualized a large-scale survey to examine the current realities of HBPM. A cross-sectional survey was conducted among health care professionals from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam between November 2019 and June 2021. Physicians' responses were summarized using descriptive statistics. A total of 7945 physicians participated in the survey. Among all respondents, 50.3% and 33.5% viewed HBPM as highly recognized by physicians and patients in their country/region, respectively. Lack of understanding of HBPM and concern with the accuracy and reliability of HBPM devices were identified as key barriers to HBPM recognition. Nearly all physicians (95.9%) reported recommending HBPM to their patients; however, they reported less than 50% of their patients measured home blood pressure (HBP). Among physicians who recommended HBPM, only 22.4% and 54.1% cited HBP diagnostic threshold values and timing of taking antihypertensive drugs that were consistent with available guidelines, respectively. The survey reveals that the recognition of HBPM as a valuable tool to diagnose and manage hypertension is suboptimal in most parts of Asia. Despite high recommendation of HBPM to hypertensive patients by physicians, there are considerable discrepancies between guidelines recommendations and practice realities. The recognition of HBPM as a valuable tool for the diagnosis and management of hypertension is suboptimal among both physicians and patients in Asia. A clear and consistent guidance for proper HBPM practice and use of validated and calibrated HBP monitors are among the top priorities to support the integration of HBPM into daily patient care. HBPM: home blood pressure monitoring, HBP: home blood pressure.
Recent innovations in digital technology have enabled the simultaneous accumulation, and the linking and analysis of time-series big data relating to several factors that influence blood pressure (BP), including biological indicators, physical activity, and environmental information. Various approaches can be used to monitor BP: in the office/clinic; at home; 24-h ambulatory recording; or with wearable and cuffless devices. Of these, home BP monitoring is a reliable and convenient method, and is recommended for hypertension management by current national and international guidelines. This recommendation is based on evidence showing that home BP is an important predictor of cardiovascular, cerebrovascular and kidney disease in patients with hypertension. In addition, lifetime personalized health record (PHR)-based home BP with telemonitoring combined with co-interventions has been shown to lower BP more effectively than the traditional approach based on office BP. Thus, home BP represents a key metric for personalized anticipation medicine, from digital healthcare to digital medicine. This paper summarizes the latest evidence on home BP monitoring and proposes a Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network consensus on a home BP-centered approach to the management of hypertension.
Resistant hypertension is a well-recognised clinical challenge. However, the definition and epidemiology of true resistant hypertension (RH) are less understood, especially in Asia. This cross-sectional study examined the prevalence of RH referred from primary care clinics based on various guidelines. RH was defined as blood pressure (BP) being above the threshold using ambulatory blood pressure monitoring despite adequate lifestyle measures and optimal treatment with ≥3 medications at maximally tolerated doses. Between one in four (n = 94, 24.0% using Malaysian guidelines) and up to two-thirds (n = 249, 63.7% using 2018 American guidelines) of adults referred for uncontrolled hypertension met the criteria of true RH. Of those with RH, a further one-quarter (n = 26, 26.6%) were deemed to have refractory hypertension (elevated BP despite treatment with at least 5 antihypertensive medications). Adults with RH were generally younger, more likely to be male, had a higher BMI and were more likely to have gout, CKD, and angina compared to those with controlled hypertension. The prevalence of RH amongst Asian adults with poor hypertension control is high. A concerted effort is needed to reduce the high burden of RH, especially among this population.