Development Of Antihypertensive Drugs Research Articles

Leptin Receptors can be an Alternative Target for New Anti-hypertensive Drug Development.

Leptin Receptors can be an Alternative Target for New Anti-hypertensive Drug Development.

Establishment of transgenic lettuce plants producing potentially antihypertensive ShRNA

Development of RNAi-based therapeutics is a fast growing field of the pharmaceutical industry. Using plants for production of pharmaceutically valuable siRNAs may have significant advantages of costeffectiveness, scalability, and low risk of contamination with human pathogens. If edible plant species are genetically engineered to synthesize siRNAs, the costly stage of target product purification may be omitted. We describe the establishment of transgenic lettuce plants producing shRNA targeting delta isoform of protein kinase C (PKC-delta), an effective target for RNAi-based treatment of arterial hypertension. Transgenic lettuce plants were obtained by Agrobacterium-mediated transformation with genetic constructs harboring antiPKC and scrambled (control) shRNA genes. The presence of transgenes was proven by PCR analysis, and the accumulation of antiPKC shRNA was estimated using the RT-qPCR technique. Six transgenic lettuce lines showed varying levels of antiPKC shRNA expression with the highest value reaching 14 ± 9% of highly abundant endogenous lettuce micro RNA (miR156a), or 12.7 fmol/g dry weight. Plants carrying either antiPKC or scrambled shRNA genes flowered normally but did not produce seeds. The described transgenic lettuce plants accumulating antiPKC siRNA are the subject for animal testing and can be considered as raw material for the development of novel antihypertensive drugs.

Drug Treatment of Hypertension: Focus on Vascular Health.

Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure (BP) elevation, the vascular system is particularly important because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high BP have greater efficacy for reducing cardiovascular risk than drugs that reduce BP, but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme ACE inhibitors (ACEIs) and angiotensinII receptor blockers (ARBs) improve endothelial function and prevent vascular remodelling. Calcium channel blockers also improve endothelial function, although to a lesser extent than ACEIs and ARBs. Mineralocorticoid receptor blockers improve endothelial function and reduce arterial stiffness, and have recently become more established as antihypertensive drugs. Lifestyle factors are essential in preventing the adverse vascular changes associated with high BP and reducing associated cardiovascular risk. Clinicians and scientists should incorporate these factors into treatment decisions for patients with high BP, as well as in the development of new antihypertensive drugs that promote vascular health.

Imperatorin derivative OW1 inhibits the upregulation of TGF-β and MMP-2 in renovascular hypertension-induced cardiac remodeling.

Chronic hypertension induces vascular and cardiac remodeling. OW1 is a novel imperatorin derivative that was previously reported to inhibit vascular remodeling and improve kidney function affected by hypertension. In the present study, the effect of OW1 on the cardiac remodeling induced by hypertension was investigated. OW1 inhibited vascular smooth muscle cell (VSMC) proliferation and the phenotypic modulation of VSMCs induced by angiotensin II (Ang II). The OW1-induced vasodilatation of rat cardiac arteries was evaluated in vitro. Renovascular hypertensive rats were developed using the two-kidney one-clip method and treated with OW1 (40 or 80 mg/kg/day) or nifedipine (30 mg/kg per day) for 5 weeks. OW1 markedly reduced the systolic and diastolic blood pressure compared with that in the hypertension group or the respective baseline value during the first week. OW1 also reduced cardiac weight, and the concentrations of Ang II, aldosterone and transforming growth factor-β1 (TGF-β1). Histological examination demonstrated that OW1 exerted an inhibitory effect on vascular and cardiac remodeling. These inhibitory effects were associated with decreased cardiac levels of Ang II, matrix metalloproteinase-2 and TGF-β1 in the hypertensive rats. In summary, OW1 exhibited a clear antihypertensive effect. More importantly, it inhibited vascular and cardiovascular remodeling, which may reduce the risk of hypertension-induced cardiovascular diseases. These results have potential implications in the development of new antihypertensive drugs.

Denatonium and 6-n-Propyl-2-thiouracil, Agonists of Bitter Taste Receptor, Inhibit Contraction of Various Types of Smooth Muscles in the Rat and Mouse.

Recently the global expression of taste 2 receptors (TAS2Rs) on smooth muscle cells in human airways was demonstrated. Here, the effects of agonists of taste receptor, type 2, denatonium and 6-n-propyl-2-thiouracil, on smooth-muscle contraction were examined in the rat and mouse. Contractions induced by carbachol (CCh), high K(+), and sodium fluoride, but not calyculin-A, were inhibited significantly in the presence of a TAS2R agonist in the bronchial smooth muscle of mice. The contraction induced by CCh was inhibited by TAS2R agonists in ileal smooth muscle. Phenylephrine-induced contraction was also inhibited by TAS2R agonists in aortic smooth muscle. Gastrointestinal motility and blood pressure were attenuated by administration of TAS2R agonists in vivo. These findings suggest that TAS2R may be receptor for endogenous biologically active substances as well as for bitter tastes on the tongue. TAS2R signaling could be employed in the development of anti-asthmatic, anti-spasmodic, and anti-hypertensive drugs.

Antihypertensive Drugs and Diabetic Retinopathy in Patients with Type 2 Diabetes

Objective: To evaluate the association between the development of sight-threatening diabetic retinopathy (STDR) and antihypertensive drugs (AHDs) use among type 2 diabetic patients with concomitant hypertension. Methods: Type 2 diabetic patients aged 20-100 years who had at least one prescription for AHDs between 2000 and 2011 were identified from the Longitudinal Health Insurance Database (LHID) 2005. The incidence rates of STDR were followed and Cox proportional hazard models were used to analyze the risk associated with AHDs. Results: Users of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were associated with a significantly higher risk than users of calcium channel blockers (CCBs), independent of baseline characteristics. After adjusting for time-varying use of concomitant medications for propensity score-matched or -unmatched cohorts, the results showed that patients receiving ACEIs/ARBs and CCBs were associated with a significantly greater risk compared with β-blocker users. Conclusions: Our study did not support a superiority of ACEIs/ARBs and CCBs over β-blockers for lowering the progression of diabetic retinopathy.

3D-QSAR studies and pharmacophore identification of AT1 receptor antagonists

A 3D-QSAR model using the GRIND/ALMOND descriptors has been performed on a set of 49 angiotensin receptor blockers, also known as angiotensin II receptor antagonists, a family of agents that bind to and inhibit the angiotensin II type 1 receptor. The most commonly used chemical probes: DRY (hydrophobic interaction), O (carbonyl oxygen sp2, hydrogen bond donor), N1 (NH neutral, hydrogen bond acceptor) and TIP (shape descriptor molecular forms) were derived from the GRID molecular interaction fields. A statistical approach was undertaken using the method of partial least squares within the Pentacle program. The results show satisfactory accuracy of the prediction model (RMSEE = 0.239, R2 = 0.94, Q2 = 0.85). The V597 (DRY-TIP) and V763 (O-TIP) represent the most significant variables that correlate positively with the activity of the ARBs. Thirty novel structures of ARBs were designed, according to the developed 3D-QSAR model and pharmacophore, what might set the basis for development of new antihypertensive drugs.

ChemInform Abstract: Synthesis of 2‐Substituted (2R,4R)‐3‐(3‐Mercapto‐propionyl)thiazolidine‐4‐carboxylic Acids.

AbstractA stereoselective three‐step synthesis of the title thiazolidine‐4‐carboxylic acids (III), potential lead compounds for the development of antihypertensive drugs with angiotensin converting enzyme inhibitory activity, starting from natural L‐cysteine (I) is given.

Molecular pathophysiology of Bartter's and Gitelman's syndromes.

In the last two decades, progress in cytogenetic and genome research has enabled investigators to unravel the underlying molecular mechanisms of inherited tubulopathies such as Bartter's and Gitelman's syndromes and helped physicians to better understand not only these two pathologic entities but also renal pathophysiology and salt sensitive hypertension. Articles collected from PubMed and open access journals included original articles, research articles, and comprehensive reviews. They were evaluated by the authors with an special emphasis on originality and up to date information about molecular pathophysiology. Bartter's and Gitelman's syndromes are two different inherited salt loosing tubulopathies. They are characterized by various inability of distal nephron to reabsorb sodium chloride with resultant extarcellular volume contraction and increased activity of the renin angiotensin aldosterone system. Hypokalemic metabolic alkalosis is a common feature of these two forms of tubulopathies. Hypercalciuria characterizes the majority of Bartter's syndrome, and hypomagnesemia with hypocalciuria characterizes Gitelman's syndrome. Low blood pressure is a common feature among patients who suffered from these tubulopathies. Bartter's syndromes encompass a heterogeneous group of ion channels defects localized at the thick ascending limp of Henle's loop with resultant loss of function of sodium-potassium-2 chloride cotransporter. These defects result in the impairment of the countercurrent multiplication system of the kidney as well as calcium, potassium and acid base disturbances which in the majority of cases are proved lethal especially in the antenatal and/or immediate postnatal life period. The underlying pathology in Gitelman's syndrome is defined to the distal convoluted tubule and is related to loss of function of the sodium-chloride cotransporter. The results of this defect encompass the inability of extracellular volume homeostasis, magnesium and potassium conservation, and acid base disturbances which are generally mild and in the majority of cases are not life-threatening. Recent advances in molecular pathophysiology of Bartter's and Gitelman's syndromes have helped physicians to better understand the underlying mechanisms of these pathologic entities which remain obscure. Data collected from experiments among genetically manipulated animals enable us to better understand the pathophysiology of mammalian kidney and the underlying mechanisms of salt sensitive hypertension and to lay a foundation for the future development of new drugs, especially diuretics and antihypertensive drugs.

Bilateral nephrectomy for uncontrolled hypertension in hemodialysis patient: A forgotten option?

Resistant arterial hypertension in chronic hemodialysis patients is still a therapeutical challenge despite the development of modern antihypertensive drugs and dialysis procedures. Bilateral nephrectomy seems to be a forgotten option, although it has given good results. We present a case of a 39-year-old female chronic hemodialysis patient, in whom the problem of uncontrolled renal parenchymal hypertension remained despite multiple drug therapy and the ultrafiltration intensification. The problem was solved by bilateral nephrectomy. We discuss the role of bilateral nephrectomy for arterial hypertension control in chronic hemodialysis patients and the surgical and non-surgical options of nephrectomy.

Relación entre el fármaco antihipertensivo utilizado y la aparición de fibrilación auricular en los pacientes hipertensos de un centro de Atención Primaria

IntroductionAlthough antihypertensive treatment can reduce the risk of cardiovascular morbimortality, studies aimed at evaluating the association between antihypertensive drug use and incidence of atrial fibrillation (AF) yield mixed results. This study aimed to determine the possible relationship between antihypertensive drug use and development of AF. Material and methodsCase control study. Cases: Hypertensive patients with AF diagnosed at least one year after the start of drug treatment for hypertension. Controls: Hypertensive patients without AF with pharmacological antihypertensive treatment for at least one year, matching by sex, age and duration of antihypertensive therapy at diagnosis of AF cases. The study included 136 cases and 132 controls. Variables: AF, antihypertensive drugs, control of hypertension, duration of treatment with antihypertensive drugs, number of antihypertensive drugs. Analysis: Crude OR were calculated, with logistic regression being used to calculate the adjusted odds ratios. ResultsOverall, diuretics was close to statistical significance: OR 0.616 (95% CI 0.365 to 1.040), as a protective factor for development of AF. Calcium channel blockers behaved as a protective factor against development of AF at 75 years or older (OR 0.366; 95% CI 0.173 to 0.772), and within this age in women (OR 0.343; 95% CI 0.145-0.811). ConclusionsCalcium channel blockers in the group of 75 years or more, especially in women, worked statistically significant as a drug protecting against the appearance of AF. Diuretics may have a protective role in AF incidence in all hypertensive patients.

Clinical Implications

HomeHypertensionVol. 62, No. 6Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Dec 2013https://doi.org/10.1161/01.hyp.0000437768.24806.faHypertension. 2013;62:981Nutrition and Higher Blood Pressure in Blacks (page 1074)For decades, the high rate of prehypertension/hypertension among adult black women and men has been a major unresolved challenge and problem for American medicine, alleviated to a limited degree by development of antihypertensive drugs but with continued expression in excess cardiovascular morbidity, disability, and premature death in blacks. The population-based data presented here imply that improved nutrition can play a role in preventing and controlling adverse blood pressure. In particular, for people, generally (including blacks), appropriate dietary emphases encompass vegetables, fruits, whole grains, legumes, fish and shellfish, low-fat and fat-free dairy products, egg whites, low-fat poultry, unprocessed lean red meats on occasion; portion sizes modest, not huge; olive oil and seed oils in modest amounts; food products uniformly low-salt or no salt, no addition of salt in the kitchen or at the table; alcoholic beverages (if desired) in modest amounts (eg, a glass of wine with one meal per day); dietary de-emphases: fatty meats, processed meats, high-fat dairy products, commercial baked goods (cakes, cookies, pies), pickled and other high-salt products, egg yolks, “hard” spreads (butter, “hard” margarines), and oils high in saturated fat (eg, coconut oil, palm oil).Physicians should do all they can, in both their medical care and public health roles, to counsel and assist all blacks to enjoy the pleasures of the table heart-healthy style at all stages of their lives.Hypertension Risk in Young Adults (page 1015)Download figureDownload PowerPointIn the United States, 29% of adults have hypertension and an additional 28% have prehypertension. Prehypertension was added to national guidelines as an official blood pressure classification within the past decade, but this classification may not be sufficient for identifying those at high risk for hypertension. In this issue of Hypertension, Carson et al investigated the predictive ability of the Framingham Heart Study (FHS) hypertension risk prediction model, which includes demographic and clinical parameters that are routinely collected in clinical practice, and compared its performance with the prehypertension classification alone in a cohort of young adults. They demonstrated that the FHS model of age, sex, systolic blood pressure, diastolic blood pressure, body mass index, cigarette smoking, and parental history of hypertension performed better than the prehypertension alone model for predicting who would and would not develop incident hypertension during the 25-year follow-up period. The FHS model performed well for both blacks and whites in the community-based Coronary Artery Risk Development in Young Adults Study; however, the predicted hypertension risk obtained from the FHS model had to be calibrated for use in the young adult population. This suggests that the FHS model may need to be calibrated when applying it to other populations. These findings highlight the benefit of using demographic and clinical parameters to improve hypertension risk assessment and the ongoing need for preventive measures.Endostatin, Hypertension Duration, and Organ Damage (page 1146)Endostatin is a biologically active derivate of collagen XVIII, which has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. Previous experimental studies have suggested a role of endostatin in the development of cardiovascular disease, and recent observational studies have shown that higher circulating endostatin is associated with an increased risk for cardiovascular events in patients with stroke and recently also in the community-based setting. Yet to date, the role of endostatin in long-term hypertension and hypertensive target organ damage has not been reported. In this issue of Hypertension, Carlsson et al report an association between longer duration of hypertension and higher serum levels of endostatin in 2 independent community-based cohorts. Participants with >27-year history of hypertension had the highest endostatin levels. Interestingly, in participants with prevalent hypertension, cross-sectional associations between higher circulating endostatin and impaired endothelial function, increased left ventricular mass and higher urinary albumin/creatinine ratio were found. These data provide additional support for the importance of increased extracellular remodeling in hypertensive disease and put forward serum endostatin as a novel promising biomarker for vascular, myocardial, and renal hypertensive organ damage. Additional studies are warranted to investigate the underlying mechanisms of these associations and to evaluate whether circulating endostatin levels can be a clinically relevant biomarker for subclinical cardiovascular damage used to identify hypertensive individuals at particularly increased cardiovascular risk. Previous Back to top Next FiguresReferencesRelatedDetails December 2013Vol 62, Issue 6 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/01.hyp.0000437768.24806.fa Originally publishedDecember 1, 2013 PDF download Advertisement

Hypertension: is it more than just a numbers game?

Hypertension: is it more than just a numbers game?

New drug therapies interfering with the renin–angiotensin–aldosterone system for resistant hypertension

There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.

High-throughput fluorescent-based NKCC functional assay in adherent epithelial cells.

BackgroundThe kidney-specific NKCC cotransporter isoform NKCC2 is involved in the Na+ reabsorption in the Thich Ascending Limb (TAL) cells and in the regulation of body fluid volume. In contrast, the isoform NKCC1 represents the major pathway for Cl- entry in endothelial cells, playing a crucial role in cell volume regulation and vascular tone. Importantly, both NKCC isoforms are involved in the regulation of blood pressure and represent important potential drug targets for the treatment of hypertension.ResultsTaking advantage of an existing Thallium (Tl+)-based kit, we set up a Tl+ influx-based fluorescent assay, that can accurately and rapidly measure NKCC transporter activity in adherent epithelial cells using the high-throughput Flex station device. We assessed the feasibility of this assay in the renal epithelial LLC-PK1 cells stably transfected with a previously characterized chimeric NKCC2 construct (c-NKCC2). We demonstrated that the assay is highly reproducible, offers high temporal resolution of NKCC-mediated ion flux profiles and, importantly, being a continuous assay, it offers improved sensitivity over previous endpoint NKCC functional assays.ConclusionsSo far the screening of NKCC transporters activity has been done by 86Rb+ influx assays. Indeed, a fluorescence-based high-throughput screening method for testing NKCC inhibitors would be extremely useful in the development and characterization of new anti-hypertensive drugs.

Experimental models of melatonin-deficient hypertension

Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs.

Characterization of an Antihypertensive Angiotensin I-Converting Enzyme Inhibitory Peptide from the Edible MushroomHypsizygus marmoreus

Hypertension is one of the very serious diseases and, recently, hypertensive patient longevity has been increased significantly. Therefore, the development of new antihypertensive drugs or bioactive compounds is very important to remedy or prevent hypertension. The antihypertensive angiotensin I-converting enzyme (ACE) inhibitor in water extracts from the brown-cultivar-fruiting-body of Hypsizygus marmoreus was purified with ultrafiltration, C18 solid phase extraction chromatography and reverse-phase HPLC, and the purified ACE inhibitor with inhibitory activity of IC50 value of 0.19 mg/mL was obtained. The purified ACE inhibitor was found to be a new oligopeptide with the sequence LSMGSASLSP. Its molecular weight was estimated to be 567.3 Da and the water extracts containing ACE inhibitor from Hypsizygus marmoreus showed a clear antihypertensive action a spontaneously hypertensive rat.

Differential gene expression profiles in spontaneously hypertensive rats induced by administration of enalapril and nifedipine

Enalapril and nifedipine are used as antihypertensive drugs; however, the therapeutic target molecules regulated by enalapril and nifedipine have yet to be fully identified. The aim of this study was to identify novel target genes that are specifically regulated by enalapril and nifedipine in tissues from spontaneously hypertensive rats (SHR) using DNA microarray analysis. We found that administration of SHR with enalapril and nifedipine differentially regulated 33genes involved in the pathogenesis of cardiovascular diseases. Furthermore, we identified 16 genes that have not previously been implicated in cardiovascular diseases, including interleukin-24 (IL-24). Among them, exogenous administration of IL-24 attenuated the expression of vascular inflammation and hypertension-related genes induced by H2O2 treatment in mouse vascular smooth muscle (MOVAS) cells. This study provides valuable information for the development of novel antihypertensive drugs. In addition, the genes identified may be of use as biomarkers and therapeutic targets for cardiovascular diseases, including hypertension.

Fixed-dose combination therapy of candesartan cilexetil and amlodipine besilate for the treatment of hypertension in Japan

Hypertension is one of the most prevalent disorders and the largest contributor to global mortality. The aim of antihypertensive treatment is to reduce the risk of cardiovascular morbidity and mortality by lowering increased blood pressure (BP) to target levels. Despite progress in antihypertensive drug development, BP control remains suboptimal. Accumulating evidence has shown that fixed-dose combination therapy is better in terms of BP control than increasing the dose of one drug or its corresponding combination. Fixed-dose combinations of an angiotensin receptor blocker, candesartan cilexetil, and a calcium channel blocker, amlodipine besilate (candesartan/amlodipine 8/2.5 or 8/5 mg), were approved in Japan for once-daily oral administration in hypertensive patients. Recent data showed that a fixed-dose combination of candesartan and amlodipine lowered BP safely and rapidly, providing a potential opportunity to improve the rate of BP control. Further studies are needed to determine whether this will lead to improvements in long-term clinical outcomes.

More about plasma renin and cardiovascular mortality

This editorial refers to ‘Association of plasma renin with 10-year cardiovascular mortality, sudden cardiac death, and death due to heart failure’, by A. Tomaschitz et al. doi:10.1093/eurheartj/ehr150. Renin, the renal pressor substance, was discovered and described by Tigerstedt and Bergman in classic experiments published in 1898. It was not, however, until 1934 that Goldblatt identified the relevance of renin by showing that renal secretion of renin caused sustained renovascular hypertension in dogs. Others subsequently demonstrated that renin itself is not the pressor element, but rather is the rate-limiting component of the newly defined renin–angiotensin–aldosterone control system (RAAS).1 This RAAS has since become recognized as a key regulator of blood pressure control and a participating factor in its pathological consequences. In the past half century, the role of the RAAS in the pathophysiology of hypertension and as a basis for antihypertensive drug development was established.2,3 Plasma renin has also been associated with cardiovascular morbidity and mortality in hypertensive patients ( Figure 1 ).4,5 Tomaschitz et al. have now extended that finding to patients in whom plasma renin was measured while taking antihypertensive drugs.6 Figure 1 Adapted by permission from Macmillan Publishers Ltd: American Journal of Hypertension , Michael H. Alderman, Wee Lock Ooi, Hillel Cohen, Shantha Madhavan, Jean E. Sealey, John H. Laragh, Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients, copyright (1997). Tomaschitz et al. measured the plasma renin concentration (PRC) using a sensitive automated immunoreactive chemiluminscence method that is comparable with the more traditional enzyme kinetic radioimmunoassay renin activity (PRA) assay. An exception is …