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Method optimization to assess endothelial function in females-duration of glyceryl trinitrate effect

Ibrahim NN, Rasool AH, Wong AR, Rahman AR

Methods Find Exp Clin Pharmacol, 2007 Jun;29(5):349-52.
PMID: 17805437

Pulse-wave analysis (PWA) combined with pharmacological challenges has recently been used as a method to measure endothelial function. This involved administration of glyceryl trinitrate (GTN), followed by salbutamol as endothelium-independent and -dependent vasodilators, respectively. The duration of GTN effect needs to be established before the administration of salbutamol. Baseline augmentation index (AIx) and pulse-wave velocity (PWV) measurements were taken in 11 healthy female subjects (mean age 23.27 +/- 3.66 years). Sublingual GTN 0.5 mg was administered for 3 min, followed by AIx and PWV measurements every 5 min till 20 min and then every 10 min until 40 min post-GTN. Maximum change in AIx post-GTN was at 3 min with a mean change from the baseline of -17.86% +/- 4.40% (p < 0.001). There were no significant changes noted after 30 and 40 min with mean change being -0.82% +/- 2.61% and 0.14% +/- 3.20%, respectively (p > 0.05). Significant changes in PWV were noted at 5 and 10 min with the mean change of -0.33 +/- 0.36 m/s and -0.33 +/- 0.35 m/s, respectively (p = 0.01). There were no further changes noted at 15 min and thereafter (p > 0.05). A duration of at least 30 min after GTN is required for AIx and PWV values to reach their baseline. Thus, the administration of salbutamol should be given only after 30 min of sublingual GTN for the assessment of endothelial function.

Matched MeSH terms: Vasodilator Agents/administration & dosage*
Fulltext Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience

Goh AY, Lum LC, Roziah M

Med J Malaysia, 2001 Sep;56(3):336-40.
PMID: 11732080

Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia.

Matched MeSH terms: Vasodilator Agents/administration & dosage*
The effectiveness of transmeatal low-power laser stimulation in treating tinnitus

Ngao CF, Tan TS, Narayanan P, Raman R

Eur Arch Otorhinolaryngol, 2014 May;271(5):975-80.
PMID: 23605244 DOI: 10.1007/s00405-013-2491-3

The aim of this study is to examine the effectiveness of transmeatal low-power laser stimulation (TLLS) in treating tinnitus. This is a prospective, double-blinded, randomized, placebo-controlled trial. Patients with persistent subjective tinnitus as their main symptom were recruited into the study from the outpatient clinics. The recruited patients were randomized into the experimental group or TLLS+ group (patients in this group were prescribed to use TLLS at 5 mW at 650 nM wavelength for 20 min daily and oral betahistine 24 mg twice per day for a total of 10 weeks) and the control group or TLLS- group (patients in this group were prescribed with a placebo device to use and oral betahistine 24 mg twice per day for 10 weeks). All patients were required to answer two sets of questionnaires: the Tinnitus handicap inventory (THI) and visual analogue scales (VAS) symptoms rating scales, before starting the treatment and at the end of the 10-week treatment period. The total score of the THI questionnaire was further graded into five grades, grade 1 being mild and grade 5 being catastrophic. Wilcoxon-signed ranks test and Mann-Whitney test were used to compare and analyze the THI and VAS scores before and after treatment for each group. Changes with p value of <0.05 were considered as statistically significant. Chi square test was used to analyze the change of parameters in categorical forms (to compare between TLLS+ and TLLS-). Changes with p value of <0.05 were considered as statistically significant. Forty-three patients successfully and diligently completed their treatment. It was noted that using any condition of the device, TLLS+ or TLLS-, patient's tinnitus symptoms improved in terms of THI scores (TLLS+, p value = 0.038; TLLS-, p value = 0.001) or VAS scores with a change of at least one grade (TLLS+, p value = 0.007; TLLS-, p value = 0.002) at p value <0.05 significant level. In contrast when TLLS+ group was compared with TLLS- group, no statistically significant result was obtained. In term of VAS scores, there seems to be no statistically significant improvement in patients' annoyance, sleep disruption, depression, concentration and tinnitus loudness and pitch heard between the two groups. Transmeatal low-power laser stimulation did not demonstrate significant efficacy as a therapeutic measure in treating tinnitus.
Study site: Otorhinolaryngology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Vasodilator Agents/administration & dosage
Sildenafil as treatment for Human Immunodeficiency Virus-related pulmonary hypertension in a child

Wong AR, Rasool AH, Abidin NZ, Noor AR, Quah BS

J Paediatr Child Health, 2006 Mar;42(3):147-8.
PMID: 16509918

Human Immunodeficiency Virus (HIV)-related pulmonary hypertension is a relatively rare disease that can affect HIV sufferers. This is almost always associated with a poor outcome and death. An 18 month-old girl, probably the youngest on record, was diagnosed to have pulmonary hypertension (PHT) and retrospectively found to have HIV infection. Sildenafil was used to control her PHT and she remains alive even after 2 years.

Matched MeSH terms: Vasodilator Agents/administration & dosage*
Mechanisms of Action of Uncaria rhynchophylla Ethanolic Extract for Its Vasodilatory Effects

Loh YC, Ch'ng YS, Tan CS, Ahmad M, Asmawi MZ, Yam MF

J Med Food, 2017 Sep;20(9):895-911.
PMID: 28771084 DOI: 10.1089/jmf.2016.3804

Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.

Matched MeSH terms: Vasodilator Agents/administration & dosage*
Fulltext Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn

Boo NY, Rohana J, Yong SC, Bilkis AZ, Yong-Junina F

Singapore Med J, 2010 Feb;51(2):144-50.
PMID: 20358154

The aim of this study was to compare the response and survival rates of term infants with persistent pulmonary hypertension of the newborn (PPHN) on high frequency oscillatory ventilation (HFOV) treated with either inhaled nitric oxide (iNO) or intravenous magnesium sulphate (MgSO4).

Matched MeSH terms: Vasodilator Agents/administration & dosage*
Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury

Tan PS, Genc F, Delgado E, Kellum JA, Pinsky MR

Intensive Care Med, 2002 Aug;28(8):1064-72.
PMID: 12185426

We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx).

Matched MeSH terms: Vasodilator Agents/administration & dosage*
Fulltext Early outcome of congenital diaphragmatic hernia in a Malaysian tertiary centre

Rohana J, Boo NY, Thambidorai CR

Singapore Med J, 2008 Feb;49(2):142-4.
PMID: 18301842

This prospective observational study was conducted to determine the outcome of newborns with congenital diaphragmatic hernia (CDH). They were managed with a protocol of gentle ventilation to avoid barotraumas, and inhaled nitric oxide (iNO) or intravenous magnesium sulphate for treatment of persistent pulmonary hypertension of newborns (PPHN).

Matched MeSH terms: Vasodilator Agents/administration & dosage
Impaired microvascular endothelial function in vitamin D-deficient diabetic nephropathy patients

Munisamy S, Kamaliah MD, Suhaidarwani AH, Zahiruddin WM, Rasool AH

J Cardiovasc Med (Hagerstown), 2013 Jun;14(6):466-71.
PMID: 22964652 DOI: 10.2459/JCM.0b013e3283590d3d

AIMS: This study aims to compare microvascular endothelial function between vitamin D-deficient and nondeficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive protein (hsCRP) were also measured.
METHODS: This prospective cross-sectional study involved 70 patients with diabetic nephropathy; 40 were categorized into the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50 nmol/l], whereas 30 patients were categorized to the group with deficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to determine endothelium-dependent and independent vasodilatation.
RESULTS: Mean age of patients was 56.7 ± 3.8 years; 50 were men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient group was 69.4 ± 2.9 nmol/l; the level in the vitamin D-deficient group was 42.1 ± 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in the vitamin D-deficient group compared with the vitamin D-nondeficient group (23.6 ± 2.7 versus 37.3 ± 3.8 arbitrary units, P = 0.004). No significant differences were observed between the two groups in their hsCRP levels, mean age, estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and glycosylated haemoglobin.
CONCLUSION: Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with deficient vitamin D levels compared with those with nondeficient levels.

Matched MeSH terms: Vasodilator Agents/administration & dosage
Vasodilation and Antihypertensive Activities of Swietenia macrophylla (Mahogany) Seed Extract

Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.

J Med Food, 2018 Mar;21(3):289-301.
PMID: 29420109 DOI: 10.1089/jmf.2017.4008

The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.

Matched MeSH terms: Vasodilator Agents/administration & dosage