Leenen Laboratory

Dr. Leenen’s current areas of research focus on two areas:

  • Brain mechanisms determining sympathetic hyperactivity in salt-sensitive hypertension and congestive heart failure
  • Genetic basis of salt-sensitive hypertension
Focus 

Brain Mechanisms and Sympathetic Hyperactivity in Genetic Models of Salt-sensitive Hypertension

Principal Investigator: Dr. Frans Leenen
Co- Investigators: Drs. Frederique Tesson, Balwant Tuana
Funding: Canadian Institutes of Health Research

Two distinct mechanisms contribute to the central nervous system (CNS) activation by high salt diet in genetically salt-sensitive rat strains such as Dahl S and SHR: 1) enhanced Na+-transport across the choroid plexus (CP) into the CSF and 2) enhanced sympatho-excitatory and pressor-responses to [Na+].

Our studies provided strong evidence for a novel concept: an increase in CSF[Na+] activates aldosterone and “ouabain” production and release in the hypothalamus. Activation of this neuromodulatory pathway by [Na+] is enhanced in S vs R rats and appears to increase activity in angiotensinergic sympatho-excitatory pathways. Blockade of this neuromodulatory pathway or of AT1-receptors in the CNS prevents the salt-induced hypertension in Dahl S.

Regarding mechanisms contributing to Na+-transport across the CP, by microarray we identified differential expression of four genes in the CP of Dahl S rats on both regular and high salt diet and of 39 genes only on high salt diet. We hypothesize that these differentially expressed genes will lead us to (new) mechanisms contributing to enhanced Na+-transport across the CP of Dahl S rats.

The following lines of research will be pursued in Dahl S and 2 salt-resistant control strains, Dahl R (70% identical) and the consomic strain SS.BN13 (98% identical with Dahl S):

Microarray follow-up studies
Regulation of CSF and brain tissue [Na+]

As a second hypothesis, we propose that a chronic increase in CSF[Na+] activates angiotensinergic neurons in the SFO leading to an increase in production and release of aldosterone and “ouabain” by neuro-secretory neurons in the SON and PVN. The following lines of research will be pursued mainly in Dahl S:

Effects of high salt intake on aldosterone and “ouabain” content in brain nuclei involved in cardiovascular regulation.
Forebrain areas showing an increase in aldosterone or “ouabain” will be evaluated for changes in gene expression of enzymes contributing to aldosterone or “ouabain” production.
CNS functional pathways activated by [Na+], either by high salt diet or icv infusion of Na+-rich aCSF.

Staff:
Hong-Wei Wang, MD PhD, Research Associate
Bing Huang, MD, PhD, Research Associate
 

Brain Mechanisms Determining Sympathetic Hyperactivity and Cardiac Dysfunction in Rats Post MI

Principal Investigator: Dr. Frans Leenen
Funding: Canadian Institutes of Health Research

The CNS acts as the “conductor” integrating inputs from a variety of sources in the body, which leads to activation of CNS descending pathways controlling activity of important regulators of cardiovascular homeostasis post MI (Leenen, Circ Res 2007). In the CNS a cascade of neuromodulators/neurotransmitters is involved. Currently, activation of local aldosterone production and release appears as the primary step. What stimulus increases aldosterone production and where in the CNS is still unknown.

The rapid increase in circulating angiotensin II post MI may activate neurons in forebrain circumventricular organs, particularly the SFO, and for the present grant we propose as novel hypothesis that angiotensinergic neurons projecting from the SFO activate aldosterone production and release which activates adjacent neurosecretory magnocellular neurons in the SON and PVN. The subsequent enhanced “ouabain” release lowers the membrane potential particularly of parvocellular neurons in the PVN, thereby sensitizing these neurons to e.g. AT1-receptor stimulation leading to persistent activation of descending pathways.

To address this concept the following approaches will be taken:

Assessment of gene expression for putative steroid biosynthetic pathways for aldosterone and “ouabain” in forebrain nuclei using both a candidate gene approach as well as microarray analysis for global, unbiased gene expression without and with blockade of specific mechanisms.
Assessment of functional connections, including chemical lesioning of specific nuclei to assess the chronic impact of this neuron population and microinjection of specific blockers to identify specific mechanisms in specific nuclei

Sympathetic Hyperactivity and Cardiac Remodeling and Dysfunction Post MI

Regarding the peripheral mechanisms mediating the effects of the CNS on the heart post MI, it is likely that cardiac effects of central blockades depend on prevention of the increase in cardiac sympathetic activity and associated cardiac effects, both direct ones and indirect ones via stimulation of the cardiac RAAS. However, in rats post MI, treatment with non-selective beta-blockers has only minimal effects on LV remodeling and dysfunction whereas beta1-blockers show some benefits.

Differences in loss of cardiomyocytes as a result of apoptosis may play a role. The RAAS (via AT1-receptors and MR) may induce cardiomyocyte apoptosis. beta1-receptor stimulation also induces apoptosis, whereas beta2- and alpha1-receptors stimulation are inhibitory. Gradual loss of myocytes post MI due to apoptosis is well established to occur in the non-infarcted myocardium leading to hypertrophy of remaining myocytes, and progressive decrease in LV systolic function.

We hypothesize that central blockades represent the most effective strategy to prevent inflammation and apoptosis and thereby maintain LV systolic function post MI and are significantly better than systemic beta1-blockade.

To address the above concepts the following approaches will be taken:

Assess effects of central blockades post MI
Compare effects of central blockades with those of beta1-receptor blockade post MI

This dual approach is unique for our group and critical for a better understanding of the pathophysiology and to translate new concepts into new/better mechanism-based approaches for interventions post MI to prevent myocyte loss and maintain LV function.

Staff:
Roselyn White, Laboratory Manager
Li Bi, Research Technician
Monir Ahmad, MD, Research Associate

 

Genetic Basis of Salt Sensitive Hypertension in Humans

Principal Investigators: Drs. Frederique Tesson, Frans Leenen
Co-Investigator: Alex Stewart
Funding: Canadian Institutes of Health Research

In the general population, high salt intake increases the blood pressure (BP) in the short-term and enhances the increase in BP with age. The BP response to salt is normally distributed with two extreme phenotypes--salt sensitive (SS) and salt resistant (SR), and an intermediate phenotype. As many as 50% of hypertensive patients are SS in short term studies, compared to only ~10% in the normotensive population.

In spite of numerous linkage and association studies of candidate genes for BP per se or BP response to salt, the genetic network responsible for BP variation remains elusive. Genes that are responsible for salt resistance have so far been largely ignored. A major limitation of genome-wide scan studies has been the limited assessment of both phenotype and genotype. In nearly all studies only office BPs were used. These are notoriously variable and can readily over-diagnose “white-coat hypertension”, or under-diagnose “masked hypertension”. Genome-wide scans so far have used widely spaced markers missing variations in intermediate chromosomal segments.

To overcome previous limitations, we propose to use the Affymetrix 1.8 million genetic markers array, a population of Caucasian subjects with family history of early onset hypertension, carefully phenotyped for BP response to salt, and the high throughput genotyping made possible by the Canadian Cardiovascular Genetics Centre at the Heart Institute. We hypothesize that “genes predisposing to salt-induced increases in BP can be identified by high density genome scan in a large population of men and women with early onset hypertension and a positive family history for hypertension, stratified based on the salt-response of BP on 24-hr ambulatory BP monitoring”.

To test the above hypothesis, the study has 6 specific aims:

Phase I Population

To phenotype a prospective male and female hypertensive Caucasian population of 510 subjects for BP response to salt using 24-hour ambulatory BP monitoring.
To perform the first genome wide association study for both SNPs and CNVs (copy number variation) using high-density arrays to identify novel risk chromosomal loci for high vs minimal BP response to high salt intake.

Phase II Population

To collect and phenotype a prospective large independent population of 1,500 individuals with elevated BP confirmed by 24-hour ambulatory BP monitoring and a control population of 1,500 normotensive individuals matched for sex and age.
Chromosomal loci showing an association with salt sensitive hypertension in Aim 2 will be genotyped in an independent population of 1500 cases and 1500 controls.
Loci confirmed to be associated with hypertension in Aim 4 will undergo further genotyping utilizing additional adjacent customized SNPs to identify gene candidates and evaluate the influence of combinations of alleles.
To characterize the potential role of the associated variants.

To assess salt-sensitivity of BP in the Phase I population, subjects receive instructions to lower salt intake over a two-week run-in period to ~100 mmol/day. On this restricted sodium diet for six weeks, they are randomized to salt-capsules (200 mmol/day) for either the first or second three-week period. 24-hr urine sodium excretion and 24-hr ambulatory BP (ABP) are assessed at the end of each period. In the Phase II population, all subjects are only studied once to assess 24-hr urinary sodium excretion and 24-hr ABP (off therapy for two weeks).

From a public health perspective, lowering the amount of salt added to foods is an important public health strategy. From an individual perspective, the impact of high salt intake on his/her cardiovascular system can vary from minimal to substantial and appears to a large extent genetically determined. The extent of this impact is clinically difficult to ascertain. Genetic diagnosis would be an ideal method of choice to advice life-style interventions for a particular individual. To achieve this goal, studies performing careful assessment of phenotype and genotypes are essential.

Staff:
Chelsea Kingsbury, Research Coordinator I
Natalie McInnis, Project Manager
Roselyn White, Laboratory Manager
Tracey Jackson, Lab Technician

 

RAS Blockade and Sympathetic Activity in Humans Post MI

Principal Investigators: Dr. Frans Leenen
Co-Investigators: Drs. Marcel Ruzicka, Ross Davies, Kathryn Ascah, Michel Le May
Funding: Heart and Stroke Foundation of Ontario

Post MI several mechanisms may activate CNS pathways involving the brain RAAS, leading to activation of peripheral mechanisms such as sympathetic activity, cytokines, cardiac RAAS. Blockade of the brain RAAS at the level of ACE or AT1-receptor is similarly effective in preventing activation of these peripheral mechanisms post MI. Through a variety of direct and indirect actions, sympathetic hyperactivity is a major determinant of adverse cardiovascular outcome. In patients sympathetic hyperactivity develops post MI, despite ACE inhibitor therapy (Graham et al, 2002; 2004; Notarius et al, 2007). In rats, at regular doses lipophilic, high affinity RAS blockers exhibit more effective penetration across the blood-brain barrier to cause blockade in the brain as compared to hydrophilic, low affinity blockers.

We hypothesize that in patients post MI RAS blockade based on lipophilic, high affinity blockers more effectively prevents increases in sympathetic activity than blockade based on hydrophilic, low affinity blockers, when used in regular doses. Lisinopril and losartan represent hydrophilic blockers, trandolapril and telmisartan lipophilic blockers.

Study Design: Post MI patients will be randomized to lisinopril or trandolapril and at three months losartan will be added to lisinopril, and telmisartan to trandolapril for another three months of follow-up. This combination approach is chosen as being currently the most clinically relevant and for the two treatment strategies may show larger differences in central effects as compared to high doses of each of the two ACE inhibitors when, at least in rats, differences in central effects diminish.

Patients, <80 years of age, admitted with an acute MI and persistent MI-related wall motion abnormalities three to six days after thrombolysis or PCI will be randomized to trandolapril or lisinopril titrated up to 4 mg or 40 mg daily for three months. At three months, losartan or telmisartan will be added, titrated up to 50 mg twice daily or 40 mg twice daily, for another three months, 50 patients per group will be enrolled.

Patients will undergo 2-D echocardiography before randomization to assess eligibility and for LV dimensions and global LV function. At three months (end of ACE inh mono-therapy) and at six months (end of combo-therapy), they will also be assessed for muscle sympathetic nerve activity (MSNA), and blood sampling for plasma catecholamines, components of the circulatory RAAS, BNP, and cytokines.

The primary end-point is the absolute MSNA after three months of mono-therapy followed by change in MSNA at 6 months on combination therapy. Secondary end-points include a composite clinical end-point and parameters contributing to or reflecting (i.e., markers) adverse cardiovascular outcomes.

We anticipate that compared to hydrophilic RAS blockade lipophilic RAS blockade not only more effectively lowers sympathetic hyperactivity, but also more effectively inhibits increases in plasma cytokines, cardiac extra-cellular matrix turnover, and possibly plasma BNP and plasma aldosterone. Changes in LV dimensions and ejection fraction over six months may be too modest to expect differences between the two treatment strategies.

Staff:
Natalie McInnis, Project Manager
Lisa Mouchet, Research Coordinator I
Roselyn White, Laboratory Manager

Projects 
  • Brain Mechanisms and Sympathetic Hyperactivity in Genetic Models of Salt-sensitive Hypertension
  • Brain Mechanisms Determining Sympathetic Hyperactivity and Cardiac Dysfunction in Rats Post MI
  • Genetic Basis of Salt Sensitive Hypertension in Humans
  • RAS Blockade and Sympathetic Activity in Humans Post MI

Brain Mechanisms and Sympathetic Hyperactivity in Genetic Models of Salt-sensitive Hypertension

Principal Investigator: Frans Leenen

Co- Investigators: Frederique Tesson, Balwant Tuana

Funding: Canadian Institutes of Health Research

Two distinct mechanisms contribute to the central nervous system (CNS) activation by high salt diet in genetically salt-sensitive rat strains such as Dahl S and SHR: 1) enhanced Na+-transport across the choroid plexus (CP) into the CSF and 2) enhanced sympatho-excitatory and pressor-responses to [Na+].

Our studies provided strong evidence for a novel concept: an increase in CSF[Na+] activates aldosterone and “ouabain” production and release in the hypothalamus. Activation of this neuromodulatory pathway by [Na+] is enhanced in S vs R rats and appears to increase activity in angiotensinergic sympatho-excitatory pathways. Blockade of this neuromodulatory pathway or of AT1-receptors in the CNS prevents the salt-induced hypertension in Dahl S.

Regarding mechanisms contributing to Na+-transport across the CP, by microarray we identified differential expression of four genes in the CP of Dahl S rats on both regular and high salt diet and of 39 genes only on high salt diet. We hypothesize that these differentially expressed genes will lead us to (new) mechanisms contributing to enhanced Na+-transport across the CP of Dahl S rats.

The following lines of research will be pursued in Dahl S and 2 salt-resistant control strains, Dahl R (70% identical) and the consomic strain SS.BN13 (98% identical with Dahl S):

  • Microarray follow-up studies
  • Regulation of CSF and brain tissue [Na+]

As a second hypothesis, we propose that a chronic increase in CSF[Na+] activates angiotensinergic neurons in the SFO leading to an increase in production and release of aldosterone and “ouabain” by neuro-secretory neurons in the SON and PVN. The following lines of research will be pursued mainly in Dahl S:

  • Effects of high salt intake on aldosterone and “ouabain” content in brain nuclei involved in cardiovascular regulation.
  • Forebrain areas showing an increase in aldosterone or “ouabain” will be evaluated for changes in gene expression of enzymes contributing to aldosterone or “ouabain” production.
  • CNS functional pathways activated by [Na+], either by high salt diet or icv infusion of Na+-rich aCSF.

Staff:

  • Hong-Wei Wang, MD PhD, Research Associate
  • Bing Huang, MD, PhD, Research Associate

Brain Mechanisms Determining Sympathetic Hyperactivity and Cardiac Dysfunction in Rats Post MI

Principal Investigator: Frans Leenen

Funding: Canadian Institutes of Health Research

The CNS acts as the “conductor” integrating inputs from a variety of sources in the body, which leads to activation of CNS descending pathways controlling activity of important regulators of cardiovascular homeostasis post MI (Leenen, Circ Res 2007). In the CNS a cascade of neuromodulators/neurotransmitters is involved. Currently, activation of local aldosterone production and release appears as the primary step. What stimulus increases aldosterone production and where in the CNS is still unknown.

The rapid increase in circulating angiotensin II post MI may activate neurons in forebrain circumventricular organs, particularly the SFO, and for the present grant we propose as novel hypothesis that angiotensinergic neurons projecting from the SFO activate aldosterone production and release which activates adjacent neurosecretory magnocellular neurons in the SON and PVN. The subsequent enhanced “ouabain” release lowers the membrane potential particularly of parvocellular neurons in the PVN, thereby sensitizing these neurons to e.g. AT1-receptor stimulation leading to persistent activation of descending pathways.

To address this concept the following approaches will be taken:

  • Assessment of gene expression for putative steroid biosynthetic pathways for aldosterone and “ouabain” in forebrain nuclei using both a candidate gene approach as well as microarray analysis for global, unbiased gene expression without and with blockade of specific mechanisms.
  • Assessment of functional connections, including chemical lesioning of specific nuclei to assess the chronic impact of this neuron population and microinjection of specific blockers to identify specific mechanisms in specific nuclei

Sympathetic Hyperactivity and Cardiac Remodeling and Dysfunction Post MI

Regarding the peripheral mechanisms mediating the effects of the CNS on the heart post MI, it is likely that cardiac effects of central blockades depend on prevention of the increase in cardiac sympathetic activity and associated cardiac effects, both direct ones and indirect ones via stimulation of the cardiac RAAS. However, in rats post MI, treatment with non-selective beta-blockers has only minimal effects on LV remodeling and dysfunction whereas beta1-blockers show some benefits.

Differences in loss of cardiomyocytes as a result of apoptosis may play a role. The RAAS (via AT1-receptors and MR) may induce cardiomyocyte apoptosis. beta1-receptor stimulation also induces apoptosis, whereas beta2- and alpha1-receptors stimulation are inhibitory. Gradual loss of myocytes post MI due to apoptosis is well established to occur in the non-infarcted myocardium leading to hypertrophy of remaining myocytes, and progressive decrease in LV systolic function.

We hypothesize that central blockades represent the most effective strategy to prevent inflammation and apoptosis and thereby maintain LV systolic function post MI and are significantly better than systemic beta1-blockade.

To address the above concepts the following approaches will be taken:

  • Assess effects of central blockades post MI
  • Compare effects of central blockades with those of beta1-receptor blockade post MI

This dual approach is unique for our group and critical for a better understanding of the pathophysiology and to translate new concepts into new/better mechanism-based approaches for interventions post MI to prevent myocyte loss and maintain LV function.

Staff:

  • Roselyn White, Laboratory Manager
  • Li Bi, Research Technician
  • Monir Ahmad, MD, Research Associate

Genetic Basis of Salt Sensitive Hypertension in Humans

Principal Investigators: Frederique Tesson, Frans Leenen

Co-Investigator: Alex Stewart

Funding: Canadian Institutes of Health Research

In the general population, high salt intake increases the blood pressure (BP) in the short-term and enhances the increase in BP with age. The BP response to salt is normally distributed with two extreme phenotypes--salt sensitive (SS) and salt resistant (SR), and an intermediate phenotype. As many as 50% of hypertensive patients are SS in short term studies, compared to only ~10% in the normotensive population.

In spite of numerous linkage and association studies of candidate genes for BP per se or BP response to salt, the genetic network responsible for BP variation remains elusive. Genes that are responsible for salt resistance have so far been largely ignored. A major limitation of genome-wide scan studies has been the limited assessment of both phenotype and genotype. In nearly all studies only office BPs were used. These are notoriously variable and can readily over-diagnose “white-coat hypertension”, or under-diagnose “masked hypertension”. Genome-wide scans so far have used widely spaced markers missing variations in intermediate chromosomal segments.

To overcome previous limitations, we propose to use the Affymetrix 1.8 million genetic markers array, a population of Caucasian subjects with family history of early onset hypertension, carefully phenotyped for BP response to salt, and the high throughput genotyping made possible by the Canadian Cardiovascular Genetics Centre at the Heart Institute. We hypothesize that “genes predisposing to salt-induced increases in BP can be identified by high density genome scan in a large population of men and women with early onset hypertension and a positive family history for hypertension, stratified based on the salt-response of BP on 24-hr ambulatory BP monitoring”.

To test the above hypothesis, the study has 6 specific aims:

Phase I Population

  • To phenotype a prospective male and female hypertensive Caucasian population of 510 subjects for BP response to salt using 24-hour ambulatory BP monitoring.
  • To perform the first genome wide association study for both SNPs and CNVs (copy number variation) using high-density arrays to identify novel risk chromosomal loci for high vs minimal BP response to high salt intake.

Phase II Population

  • To collect and phenotype a prospective large independent population of 1,500 individuals with elevated BP confirmed by 24-hour ambulatory BP monitoring and a control population of 1,500 normotensive individuals matched for sex and age.
  • Chromosomal loci showing an association with salt sensitive hypertension in Aim 2 will be genotyped in an independent population of 1500 cases and 1500 controls.
  • Loci confirmed to be associated with hypertension in Aim 4 will undergo further genotyping utilizing additional adjacent customized SNPs to identify gene candidates and evaluate the influence of combinations of alleles.
  • To characterize the potential role of the associated variants.

To assess salt-sensitivity of BP in the Phase I population, subjects receive instructions to lower salt intake over a two-week run-in period to ~100 mmol/day. On this restricted sodium diet for six weeks, they are randomized to salt-capsules (200 mmol/day) for either the first or second three-week period. 24-hr urine sodium excretion and 24-hr ambulatory BP (ABP) are assessed at the end of each period. In the Phase II population, all subjects are only studied once to assess 24-hr urinary sodium excretion and 24-hr ABP (off therapy for two weeks).

From a public health perspective, lowering the amount of salt added to foods is an important public health strategy. From an individual perspective, the impact of high salt intake on his/her cardiovascular system can vary from minimal to substantial and appears to a large extent genetically determined. The extent of this impact is clinically difficult to ascertain. Genetic diagnosis would be an ideal method of choice to advice life-style interventions for a particular individual. To achieve this goal, studies performing careful assessment of phenotype and genotypes are essential.

Staff:

  • Chelsea Kingsbury, Research Coordinator I
  • Natalie McInnis, Project Manager
  • Roselyn White, Laboratory Manager
  • Tracey Jackson, Lab Technician

RAS Blockade and Sympathetic Activity in Humans Post MI

Principal Investigators: Frans Leenen

Co-Investigators: Marcel Ruzicka, Ross Davies, Kathryn Ascah, Michel Le May

Funding: Heart and Stroke Foundation of Ontario

Post MI several mechanisms may activate CNS pathways involving the brain RAAS, leading to activation of peripheral mechanisms such as sympathetic activity, cytokines, cardiac RAAS. Blockade of the brain RAAS at the level of ACE or AT1-receptor is similarly effective in preventing activation of these peripheral mechanisms post MI. Through a variety of direct and indirect actions, sympathetic hyperactivity is a major determinant of adverse cardiovascular outcome. In patients sympathetic hyperactivity develops post MI, despite ACE inhibitor therapy (Graham et al, 2002; 2004; Notarius et al, 2007). In rats, at regular doses lipophilic, high affinity RAS blockers exhibit more effective penetration across the blood-brain barrier to cause blockade in the brain as compared to hydrophilic, low affinity blockers.

We hypothesize that in patients post MI RAS blockade based on lipophilic, high affinity blockers more effectively prevents increases in sympathetic activity than blockade based on hydrophilic, low affinity blockers, when used in regular doses. Lisinopril and losartan represent hydrophilic blockers, trandolapril and telmisartan lipophilic blockers.

Study Design: Post MI patients will be randomized to lisinopril or trandolapril and at three months losartan will be added to lisinopril, and telmisartan to trandolapril for another three months of follow-up. This combination approach is chosen as being currently the most clinically relevant and for the two treatment strategies may show larger differences in central effects as compared to high doses of each of the two ACE inhibitors when, at least in rats, differences in central effects diminish.

Patients, <80 years of age, admitted with an acute MI and persistent MI-related wall motion abnormalities three to six days after thrombolysis or PCI will be randomized to trandolapril or lisinopril titrated up to 4 mg or 40 mg daily for three months. At three months, losartan or telmisartan will be added, titrated up to 50 mg twice daily or 40 mg twice daily, for another three months, 50 patients per group will be enrolled.

Patients will undergo 2-D echocardiography before randomization to assess eligibility and for LV dimensions and global LV function. At three months (end of ACE inh mono-therapy) and at six months (end of combo-therapy), they will also be assessed for muscle sympathetic nerve activity (MSNA), and blood sampling for plasma catecholamines, components of the circulatory RAAS, BNP, and cytokines.

The primary end-point is the absolute MSNA after three months of mono-therapy followed by change in MSNA at 6 months on combination therapy. Secondary end-points include a composite clinical end-point and parameters contributing to or reflecting (i.e., markers) adverse cardiovascular outcomes.

We anticipate that compared to hydrophilic RAS blockade lipophilic RAS blockade not only more effectively lowers sympathetic hyperactivity, but also more effectively inhibits increases in plasma cytokines, cardiac extra-cellular matrix turnover, and possibly plasma BNP and plasma aldosterone. Changes in LV dimensions and ejection fraction over six months may be too modest to expect differences between the two treatment strategies.

Staff:

  • Natalie McInnis, Project Manager
  • Lisa Mouchet, Research Coordinator I
  • Roselyn White, Laboratory Manager
Publications 
  • Leenen FHH, Nwachuku CE, Black HR, Cushman WC, Davis BR, Simpson LM , Alderman MH, Atlas SA, Basile JN, Cuyjet AB, Dart R, Felicetta JV, Haywood LJ, Grimm RH, Jafri SZA, Proschan MA, Thadani U, Whelton PK, Wright JT. Clinical Events in High-Risk Hypertensive Patients Randomized to Calcium Channel Blocker vs. ACE-inhibitor in ALLHAT. Hypertension 48: 374-384, 2006.
  • Leenen FHH. Brain Mechanisms contributing to sympathetic hyperactivity and Heart Failure. Circulation Research (Editorial) 101:221-223, 2007.
  • B Liang, Leenen FHH. Prevention of Salt Induced Hypertension and Fibrosis by AT1-receptor Blockers in Dahl S Rats. Journal Cardiovascular Pharmacology 51:457-466, 2008.
  • Leenen FHH, Dumais J, McInnis NH, Turton P, Stratychuk L, Nemeth K, Lum-Kwong MM, Fodor G. Results of the Ontario Survey on the Prevalence and Control of Hypertension. Canadian Medical Association Journal 178:1441-1449, 2008.
  • Huang B, White R, Ahmad M, Jeng A, Leenen FHH. Central infusion of aldosterone synthase inhibitor prevents sympathetic hyperactivity and hypertension by central Na+ in Wistar rats. American Journal of Physiology 295:R166-172, 2008.
  • McInnis NH, Fodor G, Moy Lum-Kwong M, Leenen FHH. Antihypertensive medication use and blood pressure control: A community based cross sectional survey (ON-BP). American Journal of Hypertension 21:1210-1215, 2008.
  • Huang B, White R, Ahmad M, Tan J, Jeng AY, Leenen FHH. Central infusion of aldosterone synthase inhibitor attenuates LV dysfunction and remodeling in rats post MI. Cardiovascular Research 81:574-581, 2009.
  • Gabor A, Leenen FHH. Mechanisms mediating sodium-induced hypertension in the PVN of Wistar rats. American Journal of Physiology 296:R618-R630, 2009.
  • Huang BS, White R, Jeng A, Leenen FHH. Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats. American Journal of Physiology 296:R994-R1000, 2009.
  • Huang BS, Leenen FHH. The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and LV remodeling and dysfunction post MI. Current Heart Failure Reports 6:81-88, 2009.
  • Huang BS, Ahmad M, Tan J, Leenen FHH. Chronic central versus systemic blockade of AT1 receptors and LV dysfunction in rats post myocardial infarction. American Journal of Physiology 297:H968-H975, 2009
  • Amin MS, Reza E, Wang H, Leenen FHH. Sodium Transport in the Choroid Plexus and Salt Sensitive Hypertension. Hypertension 54:860-867, 2009.
Staff 

Research Associates

  • Monir Ahmad, MD
  • Hong-Wei Wang, MD PhD
  • Bing Huang, MD, PhD

Students

  • Alex Gabor, Graduate Student (PhD)
  • Shahrier Amin, Graduate Student (PhD)
  • Missale Tiruneh, Graduate Student (MSc)
  • Katherine Westcott, Graduate Student (MSc)
  • Sara Ahmadi, Graduate Student (MSc)
  • Anastasia Drobysheva, Graduate Student (MSc)

Support Staff

  • Lisa Mouchet, Research Coordinator I
  • Chelsea Kingsbury, Research Coordinator I
  • Natalie McInnis, Project Manager
  • Li Bi, Research Technician
  • Roselyn White, Laboratory Manager
  • Danielle Oja, Manager, Hypertension Unit

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