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1.
Eur J Med Res ; 28(1): 62, 2023 Feb 03.
Article in English | MEDLINE | ID: mdl-36732874

ABSTRACT

OBJECTIVE: To describe the association between hypertension and clinical outcomes in a cohort of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Thirty-seven (37) hospitals in the Philippines. PATIENTS: 10,881 patients admitted for COVID-19 from February to December 2020. MEASUREMENTS AND MAIN RESULTS: Among the 10,881 patients included in the Philippine CORONA Study, 3647 (33.5%) had hypertension. On regression analysis adjusted for confounders (age group, sex, smoking history, diabetes, chronic cardiac disease, chronic kidney disease, chronic respiratory disease, chronic neurologic disease, chronic liver disease, HIV/AIDS, and malignancy), patients with hypertension had significantly greater odds of in-hospital mortality (OR 1.33, 95% CI 1.17-1.52), respiratory failure (OR 1.99, 95% CI 1.75-2.28), ICU admission (OR 2.16, 95% CI 1.90-2.45) and severe/critical disease (OR 1.57, 95% CI 1.41-1.75), compared to patients without hypertension. The time-to-event analysis with confounder adjustment also showed that hypertension was significantly associated with shorter time-to-event outcomes of in-hospital mortality (HR 1.13, 95% CI 1.01-1.26), respiratory failure (HR 1.86, 95% CI 1.65-2.10), and ICU admission (HR 1.99, 95% CI 1.76-2.23). CONCLUSIONS: Our analysis of nationwide data confirmed previous findings that hypertension is an independent risk factor for worse clinical outcomes among patients hospitalized for COVID-19, with increased odds of in-hospital mortality, respiratory failure, ICU admission, and severe/critical COVID-19. More specific studies should be done to elucidate the impact of hypertension characteristics, such as chronicity, severity, drug therapy, and level of control on these clinical outcomes.


Subject(s)
COVID-19 , Hypertension , Respiratory Insufficiency , Humans , Philippines/epidemiology , SARS-CoV-2 , Retrospective Studies , Hypertension/complications , Hypertension/epidemiology , Risk Factors , Hospital Mortality , Intensive Care Units
3.
Hypertens Res ; 46(1): 244-252, 2023 01.
Article in English | MEDLINE | ID: mdl-36229530

ABSTRACT

Hypertension has remained the number one cause of cardiovascular death in the Philippines for over three (3) decades. Despite this finding, the burden accounted for by hypertension is investigated to a lesser extent. We performed this study to determine the socioeconomic impact of hypertension in the Philippines, and it was projected in the next 30 years. We gathered primary data through interviews, Labor Force Survey (N = 806), and secondary data from various government published reports. The cost of illness (COI) was calculated using the direct morbidity and mortality costs. The impact (% of respondents) of uncontrolled hypertension on productivity at work showed the following; four (4) days missing work (72%) and ten (10) days lost of productivity (63%). The impact (% of respondents) of uncontrolled hypertension on productivity at home showed the following: six (6) days of household suspended (66%), eleven (11) days reduced household work (78%), and five (5) days affected social activity (60%). The productivity loss of premature mortality accounts for 17% of the total economic burden in 2020 and will increase to 20% by 2050. In 2020, 70% of the total economic burden was accounted for direct & indirect care. At its present value, the economic cost of hypertension is expected to increase from US$1 billion in 2020 to US$1.9 billion by 2050. The socioeconomic impact of uncontrolled hypertension in the Philippines was enormous, challenging, and overwhelming for the next 30 years.


Subject(s)
Cost of Illness , Hypertension , Humans , Philippines/epidemiology , Surveys and Questionnaires , Hypertension/epidemiology , Socioeconomic Factors
4.
Medicine (Baltimore) ; 101(5): e28703, 2022 Feb 04.
Article in English | MEDLINE | ID: mdl-35119014

ABSTRACT

ABSTRACT: Genetic variation is known to affect response to calcium channel blockers (CCBs) among different populations. This study aimed to determine the genetic variations associated with poor response to this class of antihypertensive drugs among Filipinos.One hundred eighty one hypertensive participants on CCBs therapy were included in an unmatched case-control study. Genomic deoxyribonucleic acid were extracted and genotyped for selected genetic variants. Regression analysis was used to determine the association of genetic and clinical variables with poor response to medication.The variant rs1458038 near fibroblast growth factor 5 gene showed significant association with poor blood pressure-lowering response based on additive effect (CT genotype: adjusted OR 3.41, P = .001; TT genotype: adjusted OR 6.72, P < .001).These findings suggest that blood pressure response to calcium channels blockers among Filipinos with hypertension is associated with gene variant rs1458038 near fibroblast growth factor 5 gene. Further studies are recommended to validate such relationship of the variant to the CCB response.


Subject(s)
Antihypertensive Agents , Calcium Channel Blockers , Fibroblast Growth Factor 5/genetics , Hypertension , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Calcium Channel Blockers/therapeutic use , Case-Control Studies , Humans , Hypertension/drug therapy , Hypertension/genetics , Philippines
6.
Eur Heart J Suppl ; 23(Suppl B): B120-B123, 2021 May.
Article in English | MEDLINE | ID: mdl-34733126

ABSTRACT

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2019 (MMM19) blood pressure (BP) measurement campaign to raise awareness of hypertension especially in those who are not aware of their condition. The MMM19 standard protocol designed by the International Society of Hypertension was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken two to three times, using an automated BP apparatus and were inputted either in the MMM19 app or data were recorded in paper form and manually transferred to Excel spreadsheets by encoders supervised by the PSH. A total of 89 941 participated through opportunistic convenience sampling. After multiple imputation, a total of 47 925 (53.3%) participants had hypertension (≥140/90 mmHg or on antihypertensive medication). Of this number, 31 151 (65%) were aware that they had high BP and 30 120 (62.8%) were on antihypertensive medications. Of the 30 120 participants on antihypertensive medications, only 18 373 (61.1%) had controlled BP (<140/90 mmHg). Being overweight or obese were significant predictors of high BP. Other predictors of high systolic BP and diastolic BP were alcohol intake, smoking, and a previous history of hypertension in pregnancy, while pregnant participants had significantly lower BP. The MMM19 campaign succeeded in raising awareness of high BP in our country, and the opportunistic sampling enhanced a sense of people empowerment by their knowing how easy it is to detect high BP and thereby enabling the prevention of long-term health complications. The higher BP control in the MMM19 hypertensive individuals possibly attests to the success of the previous MMM17 and MMM18 campaigns.

7.
J Clin Hypertens (Greenwich) ; 23(9): 1637-1650, 2021 09.
Article in English | MEDLINE | ID: mdl-34343391

ABSTRACT

Hypertension is the most common cause of death and disability worldwide with its prevalence rising in low to middle income countries. It remains to be an important cause of morbidity and mortality in the Philippines with poor BP control as one of the main causes. Different societies and groups worked and collaborated together to develop the 2020 Philippine Clinical Practice Guidelines of hypertension arising for the need to come up with a comprehensive local practice guideline for the diagnosis, treatment, and follow up of persons with hypertension. A technical working group was organized into six clusters that analyzed the 30 clinical questions commonly asked in practice, looking into the definition of hypertension, treatment thresholds, blood pressure targets, and appropriate medications to reach targets. This guideline also includes recommendations for the specific management of hypertension among individuals with uncomplicated hypertension, hypertension among those with diabetes, stroke, chronic kidney disease, as well as hypertension among pregnant women and pediatric populations. It also looked into the appropriate screening and monitoring of patients when managing hypertension, and identification of groups who are at high risk for cardiovascular (CV) events. The ADAPTE process was used in developing the statements and recommendations which were then presented to a panel of experts for discussion and approval to come up with the final statements. This guideline aims to aid Filipino healthcare professionals to provide evidence-based care for persons with hypertension and help those with hypertension adequately control their blood pressure and reduce their CV risk.


Subject(s)
Hypertension , Blood Pressure , Child , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Mass Screening , Philippines/epidemiology , Pregnancy
8.
J ASEAN Fed Endocr Soc ; 36(1): 5-11, 2021.
Article in English | MEDLINE | ID: mdl-34177082

ABSTRACT

Dyslipidemia is a cardiovascular risk factor that is increasing in prevalence in the country. The need to treat and manage elevated cholesterol levels, both pharmacologic and non-pharmacologic, is of utmost importance. Different medical societies and groups bonded together to formulate the 2020 Philippine Clinical Practice Guidelines for dyslipidemia. The group raised nine clinical questions that are important in dyslipidemia management. A technical working group analyzed the clinical questions dealing with non-pharmacologic management, primary prevention for both non-diabetic and individuals with diabetes, familial hypercholesterolemia, secondary prevention, adverse events of statins and the use of other lipid parameters as measurement of risk for cardiovascular disease. Randomized controlled trials and meta-analyses were included in the GRADE-PRO analysis to come up with the statements answering the clinical questions. The statements were presented to a panel consisting of government agencies, members of the different medical societies, and private institutions, and the statements were voted upon to come up with the final statements of the 2020 practice guidelines. The 2020 CPG is aimed for the Filipino physician to confidently care for the individual with dyslipidemia and eventually lower his risk for cardiovascular disease.

9.
Eur Heart J Suppl ; 22(Suppl H): H104-H107, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32884485

ABSTRACT

Building on the gains of May Measurement Month 2017 (MMM17), the Philippine Society of Hypertension once again took part in MMM18 to raise awareness of high blood pressure (BP) in the country and to harness opportunistic BP screening in detecting unaware hypertensive individuals and referring them for treatment. We followed the standard MMM18 protocol designed by the International Society of Hypertension, utilizing convenience sampling with volunteer investigators, taking three sitting BP measurements of volunteer adults (≥18 years). Basic data on demographic, lifestyle, and environmental factors were also taken. We analysed 177 176 screened individuals from the Philippines. Of these, 29.1% (51 527) had also participated in MMM17, whereas 68.8% (121 893) were new screenees; and 14.2% (25 232) had their BP taken for the first time ever. After multiple imputation, 39.0% (69 126) were hypertensive. Of these, 50.3% (34 795) were aware they were hypertensive. 49.9% (34 491) were on antihypertensive medication, 58.0% (20 010) of whom had controlled BP <140/90 mmHg. Only 28.9% of all participants with hypertension had controlled BP. Systolic BPs and diastolic BPs were significantly higher in the overweight and obese, in those receiving antihypertensive medications, in patients with diabetes, and significantly lower in pregnant women. MMM18 has again shown that opportunistic BP screening, harnessing volunteers, is a pragmatic public health measure to improve awareness and treatment rates of raised BP.

10.
J Hypertens ; 38(12): 2369-2377, 2020 12.
Article in English | MEDLINE | ID: mdl-32833920

ABSTRACT

: The 2008 European Society of Cardiology/European Society of Hypertension guidelines recommend the first-line prescription of two antihypertensive drugs in single-pill combinations (SPCs), also known as fixed-dose combinations, for the treatment of most patients with hypertension. This recommendation is based on a large amount of data, which shows that first-line treatment with SPCs supports reaching blood pressure targets rapidly and reducing cardiovascular outcome risk while keeping the therapeutic strategies as simple as possible and fostering adherence and persistence. As this approach constitutes a big shift from the stepped-care approaches that have been dominant for many years, practicing physicians have expressed concerns about using SPCs as first-line agents. In this review, we will discuss the barriers to the uptake of this recommendation. We will also offer suggestions to reduce the impact of these barriers and address specific concerns that have been raised.


Subject(s)
Antihypertensive Agents/administration & dosage , Hypertension/drug therapy , Blood Pressure/drug effects , Cardiology , Drug Combinations , Humans , Practice Guidelines as Topic
11.
J Clin Neurosci ; 77: 234-236, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32414622

ABSTRACT

The 2019 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan, China last December 2019, has been declared an emergency by the World Health Organization but eventually progressed to become a Pandemic. To date, Coronavirus Disease 2019 (COVID-19) has affected at least 100,000 individuals worldwide, reaching thousands of mortalities (Zhou et al., 2020; World Health Organization, 2020). In the Philippines, the number of COVID-19 confirmed positive cases is over 636 and is expected to rise (Department of Health, 2020). Respiratory infections alongside their comorbidities can induce acute myocardial infarction and acute ischemic stroke (Warren-Gash et al., 2018) [3]. These may further bring challenges in the management and administration of Intravenous (IV) Alteplase in eligible patients. Currently, there are no case reports in the administration IV Altepase in ischemic stroke patients who are COVID-19 positive. We present a case of a 62-year old female who was admitted due to cough, colds and shortness of breath of 2 weeks duration and was tested to be COVD-19 positive. She suffered from an ischemic stroke while in the Medical Intensive Care Unit and was given Intravenous thrombolysis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/etiology , Thrombolytic Therapy/methods , Administration, Intravenous , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Humans , Middle Aged , Pandemics , Philippines , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Stroke/drug therapy , Stroke/virology , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use
12.
Clin Pharmacol Ther ; 107(1): 221-226, 2020 01.
Article in English | MEDLINE | ID: mdl-31350855

ABSTRACT

A common drug used for hypertension among Filipinos is beta-blockers. Variable responses to beta-blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta-blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta-blockers were enrolled in an unmatched case-control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta-blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta-blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta-blockers, which may become a potential marker to aid in the management of hypertension.


Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Antihypertensive Agents/administration & dosage , Glucuronidase/genetics , Hypertension/drug therapy , Adrenergic beta-Antagonists/pharmacology , Adult , Antihypertensive Agents/pharmacology , Case-Control Studies , Female , Genetic Variation , Genotype , Humans , Hypertension/genetics , Klotho Proteins , Male , Middle Aged , Philippines , Treatment Outcome
13.
Eur Heart J Suppl ; 21(Suppl D): D92-D96, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31043890

ABSTRACT

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population.

14.
Acta Medica Philippina ; : 49-52, 2013.
Article in English | WPRIM (Western Pacific) | ID: wpr-633669

ABSTRACT

OBJECTIVE: The prevalence of hypertension is 20% in the Philippines, and it increases year after year. It remains a risk factor for coronary heart disease, stroke, and heart and renal failure. The gravity of complications from hypertension also reflects the effectiveness of the awareness programs in the Philippines. The patient population of the Philippine General Hospital (PGH), being a tertiary referral center in the Philippines, has been represented by indigenous groups of Filipino people from the different provinces in the Philippines. In 1966, Dr. Baltazar conducted a study on the pattern of distribution of hypertension in PGH. It showed that essential hypertension was the leading cause of admission in PGH. This study aims to determine the prevalence and distribution of hypertensives admitted to PGH after for decades of improvement in the diagnosis and treatment of hypertension in the Philippines. METHODS: Chart review of all hypertensive patients admitted at the charity wards or intensive care units in PGH in 2005 was performed. The year 2005 was selected due to the limitation of the Medical Records Section in retrieving charts before that year. Data from the Department of Pediatrics was excluded due to the insignificant number of hypertensives seen by the Department. RESULTS: The information obtained from this study showed a decline in prevalence from 8.4% in 1966 to 4.1% in 2005 with a predominance of pregnancy-related hypertension in 1966 compared with primary hypertension in 2005. CONCLUSION: This comparative study shows an expected decline in the prevalence of hypertension among admitted patients which can be attributed to heightened hypertension awareness, screening programs, and good quality of care.


Subject(s)
Humans , Risk Factors , Prevalence , Hospitals, General , Tertiary Care Centers , Essential Hypertension , Hypertension , Stroke , Coronary Disease , Renal Insufficiency
15.
Acta Medica Philippina ; : 59-61, 2012.
Article in English | WPRIM (Western Pacific) | ID: wpr-633791

ABSTRACT

OBJECTIVE: To validate the Filipino version of the Berlin questionnaire (BQ) as a tool to screen for the risk of obstructive sleep apnea (OSA) in a primary care patients. BACKGROUND: Most patients with OSA are unrecognized and untreated. The BQ is a tool that has been validated to screen for patients at risk for OSA and has been translated into and used in different languages. METHOD: The forward and backward translation method was applied. The Filipino version was administered to 40 individuals able to read and understand both English and Filipino in different communities within the Metro Manila area followed 24 hours later with the English version. A focused group discussion and feedback were done after. RESULTS: The BQ in Filipino showed good construct validity supported by the Cramer's coefficient ranging from 0.802 to 1 (p CONCLUSIONS: The BQ in Filipino showed high construct validity. It can now be used as a research tool to conduct studies on risk assessment and disease correlation with OSA in the local community. It may likewise be used as a screening tool especially in areas with limited resources in order to identify patients who may need further workup for OSA.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Berlin , Translating , Translations , Sleep Apnea, Obstructive , Risk Assessment , Primary Health Care
16.
Am J Hypertens ; 22(1): 41-5, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18989257

ABSTRACT

BACKGROUND: Previous studies have shown that the presynaptic alpha(2B)-adrenoceptor subtype in the central nervous system has a sympathoexcitatory function and its activation leads to a hyperadrenergic hypertensive state. The purpose of this project was to develop a novel hyperadrenergic model, a transgenic (TG) mouse model with brain-selective overexpression of the alpha(2B)-adrenergic receptor (alpha(2B)-AR). METHODS: We used Southern blot analysis to confirm transgene, real-time PCR to assess gene expression, western Blot analysis and immunohistology to assess protein expression and localization in brain areas. Indirect blood pressure (BP) and heart rate were recorded. RESULTS: In TG mice there was a 1.8-fold increase in alpha(2B)-AR protein expression compared to wild-type (WT) mice. Immunostaining of brain sections revealed that concentration of alpha(2B)-AR was much more pronounced in TG than in WT mice. Systolic BP at 8 weeks of age was significantly elevated in TG 130 +/- 6 mm Hg, compared with WT control nontransgenic littermates of the same age 107 +/- 7 mm Hg, (P < 0.05), indicating that the TG mice had indeed developed hypertension. CONCLUSIONS: We have therefore documented that overexpression of the alpha(2B)-AR gene leads to increased production of alpha(2B)-AR protein in brain regions known to regulate central sympathetic outflow, thus resulting in sustained BP elevation. This is a unique model of experimental hypertension driven purely by overexpression of the alpha(2B)-AR that would result in an overactive sympathetic system and would be suitable for testing the pharmacologic properties of potential therapeutic agents.


Subject(s)
DNA/genetics , Gene Expression , Hypertension/genetics , Receptors, Adrenergic, alpha-2/genetics , Animals , Blood Pressure/physiology , Blotting, Southern , Blotting, Western , Brain/metabolism , Disease Models, Animal , Follow-Up Studies , Genetic Predisposition to Disease , Hypertension/metabolism , Hypertension/physiopathology , Immunohistochemistry , Male , Mice , Mice, Transgenic , Receptors, Adrenergic, alpha-2/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction
17.
Hypertension ; 51(5): 1352-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18347228

ABSTRACT

We sought to define the contribution of each of the 2 kinin receptors (bradykinin 1 receptor [B(1)R] and bradykinin 2 receptor [B(2)R]) to the cardioprotection of angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarct. Wild-type mice and gene knockout mice missing either B(1)R or B(2)R were submitted to coronary ligation with or without concurrent ACE inhibition and had evaluation of left ventricular systolic capacity by assessment of fractional shortening (FS). Baseline FS was similar in all of the animals and remained unchanged in sham-operated ones. At 3 weeks after myocardial infarct, in the wild-type group there was a 27% reduction of FS (P<0.5) without ACE inhibition and 8% with ACE inhibition; in the B(1)R(-/-) groups the FS was reduced by 24% and was no different (at 28%) with ACE inhibition; in the B(2)R(-/-) groups, however, the FS was decreased by 39% and with ACE inhibition was decreased further by 52%. Analysis of bradykinin receptor gene expression in hearts showed that when one receptor was missing, the other became significantly upregulated; but the B(1)R remained highly overexpressed in the B(2)R(-/-) mice throughout, whereas the overexpressed B(2)R became significantly suppressed in the B(1)R(-/-) mice in a manner quantitatively and directionally similar to that of wild-type mice. We conclude that both bradykinin receptors contribute to the cardioprotective bradykinin-mediated effect of ACE inhibition, not only the B(2)R as believed previously; but, whereas with potentiated bradykinin in the absence of B(1)R, the upregulation of B(2)R is simply insufficient to provide full cardioprotection, in the absence of B(2)R, the upregulated B(1)R actually seems to inflict further tissue damage.


Subject(s)
Myocardial Infarction/metabolism , Peptidyl-Dipeptidase A/metabolism , Receptor, Bradykinin B1/metabolism , Receptor, Bradykinin B2/metabolism , Animals , Blood Pressure/physiology , Chymases/metabolism , Disease Models, Animal , Heart/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III , Protein Serine-Threonine Kinases/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase
18.
Vascul Pharmacol ; 46(5): 367-72, 2007 May.
Article in English | MEDLINE | ID: mdl-17307398

ABSTRACT

Sympathetic-induced vasoconstriction is mediated by various adrenergic receptor (AR) subtypes located on membranes of vascular smooth muscle cells (VSMC) located on the arterial wall, but is mostly attributed to activation of the alpha(1D)-AR. In order to study interaction and cross-talk among AR genes, we induced post-transcriptional silencing of the alpha(1D)-AR gene in cultured VSMC using the RNAi technique. A pSEC neo expression plasmid vector containing a small interfering RNA (siRNA) sequence selected to bind to the targeted mRNA of the alpha(1D)-AR gene was transfected into cultured VSMC from rat aorta. The RNA expression of all AR-subtype genes was assessed by Q-RT-PCR and the alpha(1D) and alpha(2A)-AR proteins quantified by Western blot. In siRNA-transfected cells, the alpha(1D)-AR protein levels decreased by 55%, 69% and 75% at 24 h, 48 h and 72 h, respectively (p<0.03-0.01) with progressive increases in its gene expression by 50%-61% and concurrent increase in alpha(2A)-AR protein peaking at 48 h. Decreases were noted in expression of the alpha(1A), alpha(2A), and beta(3) AR genes. We conclude that post-transcriptional silencing of the alpha(1D)-AR gene leads to significant decrease in receptor protein despite reactive increase in gene expression. However, suppression of one AR leads to reactive changes in other subtypes, indicating that cross-talk among related genes, whose products have overlapping functions, may partly offset anticipated effects in vivo.


Subject(s)
Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , RNA Interference , Receptors, Adrenergic, alpha-1/genetics , Animals , Aorta, Thoracic/cytology , Aorta, Thoracic/metabolism , Cells, Cultured , Male , Muscle, Smooth, Vascular/cytology , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Adrenergic, beta-3/metabolism , Time Factors , Transfection
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