Full Text Journal Articles by
Author Barbara Kemp Harper

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Identifying the core concepts of pharmacology education.

Paul J White, Elizabeth A Davis, Marina Santiago, Tom Angelo, Alison Shield, Anna-Marie Babey, Barbara Kemp-Harper, Gregg Maynard, Hesham S Al-Sallami, Ian F Musgrave, Lynette B Fernandes, Suong N T Ngo, Tina Hinton,

Pharmacology education currently lacks an agreed knowledge curriculum. Evidence from physics and biology education indicates that core concepts are useful and effective structures around which such a curriculum can be designed to facilitate student learning. Building on previous work, we developed a novel, criterion-based method to identify the core concepts ... Read more >>

Pharmacol Res Perspect (Pharmacology research & perspectives)
[2021, 9(4):e00836]

Cited: 0 times

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Simultaneous targeting of oxidative stress and fibrosis reverses cardiomyopathy-induced ventricular remodelling and dysfunction.

Chao Wang, Tracey A Gaspari, Dorota Ferens, Iresha Spizzo, Barbara K Kemp-Harper, Chrishan S Samuel,

<h4>Background and purpose</h4>Oxidative stress and fibrosis are hallmarks of cardiomyopathy-induced heart failure yet are not effectively targeted by current frontline therapies. Here, the therapeutic effects of the anti-oxidant, N-acetylcysteine (NAC), were compared and combined with an acute heart failure drug with established anti-fibrotic effects, serelaxin (RLX), in a murine model ... Read more >>

Br J Pharmacol (British journal of pharmacology)
[2021, 178(12):2424-2442]

Cited: 0 times

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Animal models of pulmonary hypertension: Getting to the heart of the problem.

Joshua P Dignam, Tara E Scott, Barbara K Kemp-Harper, Adrian J Hobbs,

Despite recent therapeutic advances, pulmonary hypertension (PH) remains a fatal disease due to the development of right ventricular (RV) failure. At present, no treatments targeted at the right ventricle are available, and RV function is not widely considered in the preclinical assessment of new therapeutics. Several small animal models are ... Read more >>

Br J Pharmacol (British journal of pharmacology)
[2021, :]

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Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation.

Barbara K Kemp-Harper, Anida Velagic, Nazareno Paolocci, John D Horowitz, Rebecca H Ritchie,

Reactive oxygen species (ROS) dysregulation is a hallmark of cardiovascular disease, characterised by an imbalance in the synthesis and removal of ROS. ROS such as superoxide (•O<sub>2</sub><sup>-</sup>), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), hydroxyl (OH•) and peroxynitrite (ONOO<sup>-</sup>) have a marked impact on cardiovascular function, contributing to the vascular impairment and cardiac dysfunction ... Read more >>

Handb Exp Pharmacol (Handbook of experimental pharmacology)
[2021, 264:311-337]

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Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling.

Anida Velagic, Chengxue Qin, Owen L Woodman, John D Horowitz, Rebecca H Ritchie, Barbara K Kemp-Harper,

Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2020, 11:727]

Cited: 3 times

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The anti-fibrotic actions of relaxin are mediated through AT2 R-associated protein phosphatases via RXFP1-AT2 R functional crosstalk in human cardiac myofibroblasts.

Chao Wang, Anita A Pinar, Robert E Widdop, Mohammed A Hossain, Ross A D Bathgate, Kate M Denton, Barbara K Kemp-Harper, Chrishan S Samuel,

Fibrosis is a hallmark of several cardiovascular diseases. The relaxin family peptide receptor 1 (RXFP1) agonist, relaxin, has rapidly occurring anti-fibrotic actions which are mediated through RXFP1 and angiotensin II receptor crosstalk on renal and cardiac myofibroblasts. Here, we investigated whether this would allow relaxin to indirectly activate angiotensin II ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2020, 34(6):8217-8233]

Cited: 0 times

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Targeting the NLRP3 inflammasome to treat cardiovascular fibrosis.

Anita A Pinar, Tara E Scott, Brooke M Huuskes, Felipe E Tapia Cáceres, Barbara K Kemp-Harper, Chrishan S Samuel,

Cardiovascular fibrosis refers to the scar tissue that develops in the injured heart and blood vessels from an aberrant wound healing response to organ injury or insult. Established fibrosis becomes a hallmark of chronic disease progression and a key contributor to tissue stiffness and dysfunction, which ultimately leads to heart ... Read more >>

Pharmacol Ther (Pharmacology & therapeutics)
[2020, 209:107511]

Cited: 12 times

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Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries.

Jasmin Chendi Li, Anida Velagic, Cheng Xue Qin, Mandy Li, Chen Huei Leo, Barbara K Kemp-Harper, Rebecca H Ritchie, Owen L Woodman,

Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2020, 11:585740]

Cited: 1 time

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An in vivo examination of the differences between rapid cardiovascular collapse and prolonged hypotension induced by snake venom.

Rahini Kakumanu, Barbara K Kemp-Harper, Anjana Silva, Sanjaya Kuruppu, Geoffrey K Isbister, Wayne C Hodgson,

We investigated the cardiovascular effects of venoms from seven medically important species of snakes: Australian Eastern Brown snake (Pseudonaja textilis), Sri Lankan Russell's viper (Daboia russelii), Javanese Russell's viper (D. siamensis), Gaboon viper (Bitis gabonica), Uracoan rattlesnake (Crotalus vegrandis), Carpet viper (Echis ocellatus) and Puff adder (Bitis arietans), and identified ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):20231]

Cited: 3 times

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Nitric Oxide Resistance, Induced in the Myocardium by Diabetes, Is Circumvented by the Nitric Oxide Redox Sibling, Nitroxyl.

Cheng Xue Qin, Jarryd Anthonisz, Chen Huei Leo, Nicola Kahlberg, Anida Velagic, Mandy Li, Edwina Jap, Owen L Woodman, Laura J Parry, John D Horowitz, Barbara K Kemp-Harper, Rebecca H Ritchie,

Aim: Impairment of tissue responsiveness to exogenous and endogenous nitric oxide (NO•), known as NO• resistance, occurs in many cardiovascular disease states, prominently in diabetes and especially in the presence of marked hyperglycemia. In this study, we sought to determine in moderate and severe diabetes (i) whether NO• resistance also ... Read more >>

Antioxid Redox Signal (Antioxidants & redox signaling)
[2020, 32(1):60-77]

Cited: 5 times

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Distinct Redox Signalling following Macrophage Activation Influences Profibrotic Activity.

Caitlin V Lewis, Antony Vinh, Henry Diep, Chrishan S Samuel, Grant R Drummond, Barbara K Kemp-Harper,

Aims:To date, the ROS-generating capacities of macrophages in different activation states have not been thoroughly compared. This study is aimed at determining the nature and levels of ROS generated following stimulation with common activators of M1 and M2 macrophages and investigating the potential for this to impact fibrosis. Results:Human primary ... Read more >>

J Immunol Res (Journal of immunology research)
[2019, 2019:1278301]

Cited: 1 time

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Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension.

Shalini M Krishnan, Yeong H Ling, Brooke M Huuskes, Dorota M Ferens, Narbada Saini, Christopher T Chan, Henry Diep, Michelle M Kett, Chrishan S Samuel, Barbara K Kemp-Harper, Avril A B Robertson, Matthew A Cooper, Karlheinz Peter, Eicke Latz, Ashley S Mansell, Christopher G Sobey, Grant R Drummond, Antony Vinh,

<h4>Aims</h4>Renal inflammation, leading to fibrosis and impaired function is a major contributor to the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1β and pro-IL-18. In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure ... Read more >>

Cardiovasc Res (Cardiovascular research)
[2019, 115(4):776-787]

Cited: 42 times

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D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels.

Rahini Kakumanu, Sanjaya Kuruppu, Lachlan D Rash, Geoffrey K Isbister, Wayne C Hodgson, Barbara K Kemp-Harper,

Russell's viper (Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell's viper envenoming. The mechanism(s) responsible for this effect are unclear. In this study, we examined the cardiovascular effects of Sri Lankan D. russelii venom in anaesthetised rats and ... Read more >>

Toxins (Basel) (Toxins)
[2019, 11(4):]

Cited: 1 time

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Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding.

Rahini Kakumanu, Wayne C Hodgson, Ravina Ravi, Alejandro Alagon, Richard J Harris, Andreas Brust, Paul F Alewood, Barbara K Kemp-Harper, Bryan G Fry,

Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (<i>Desmondus ... Read more >>

Toxins (Basel) (Toxins)
[2019, 11(1):]

Cited: 3 times

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Inflammasomes: a novel therapeutic target in pulmonary hypertension?

Tara Elizabeth Scott, Barbara K Kemp-Harper, Adrian J Hobbs,

Pulmonary hypertension (PH) is a rare, progressive pulmonary vasculopathy characterized by increased mean pulmonary arterial pressure, pulmonary vascular remodelling and right ventricular failure. Current treatments are not curative, and new therapeutic strategies are urgently required. Clinical and preclinical evidence has established that inflammation plays a key role in PH pathogenesis, ... Read more >>

Br J Pharmacol (British journal of pharmacology)
[2019, 176(12):1880-1896]

Cited: 6 times

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Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization.

Cheng Huang, Caitlin Lewis, Natalie A Borg, Meritxell Canals, Henry Diep, Grant R Drummond, Robert J Goode, Ralf B Schittenhelm, Antony Vinh, Mingyu Zhu, Barbara Kemp-Harper, Oded Kleifeld, Martin J Stone,

Macrophages, which accumulate in tissues during inflammation, may be polarized toward pro-inflammatory (M1) or tissue reparative (M2) phenotypes. The balance between these phenotypes can have a substantial influence on the outcome of inflammatory diseases such as atherosclerosis. Improved biomarkers of M1 and M2 macrophages would be beneficial for research, diagnosis, ... Read more >>

J Proteome Res (Journal of proteome research)
[2018, 17(4):1485-1499]

Cited: 5 times

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Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress.

Quynh Nhu Dinh, Grant R Drummond, Barbara K Kemp-Harper, Henry Diep, T Michael De Silva, Hyun Ah Kim, Antony Vinh, Avril A B Robertson, Matthew A Cooper, Ashley Mansell, Sophocles Chrissobolis, Christopher G Sobey,

Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang ... Read more >>

Aging (Albany NY) (Aging)
[2017, 9(6):1595-1606]

Cited: 18 times

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Vasoactive actions of nitroxyl (HNO) are preserved in resistance arteries in diabetes.

Marianne Tare, Rushita S R Kalidindi, Kristen J Bubb, Helena C Parkington, Wee-Ming Boon, Xiang Li, Christopher G Sobey, Grant R Drummond, Rebecca H Ritchie, Barbara K Kemp-Harper,

Endothelial dysfunction is a major risk factor for the vascular complications of diabetes. Increased reactive oxygen species (ROS) generation, a hallmark of diabetes, reduces the bioavailability of endothelial vasodilators, including nitric oxide (NO·). The vascular endothelium also produces the one electron reduced and protonated form of NO·, nitroxyl (HNO). Unlike ... Read more >>

Naunyn Schmiedebergs Arch Pharmacol (Naunyn-Schmiedeberg's archives of pharmacology)
[2017, 390(4):397-408]

Cited: 4 times

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The opposing roles of NO and oxidative stress in cardiovascular disease.

Rebecca H Ritchie, Grant R Drummond, Christopher G Sobey, T Michael De Silva, Barbara K Kemp-Harper,

Nitric oxide (NO) plays a pivotal role in the maintenance of cardiovascular homeostasis. A reduction in the bioavailability of endogenous NO, manifest as a decrease in the production and/or impaired signaling, is associated with many cardiovascular diseases including hypertension, atherosclerosis, stroke and heart failure. There is substantial evidence that reactive ... Read more >>

Pharmacol Res (Pharmacological research)
[2017, 116:57-69]

Cited: 19 times

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Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-induced hypertension.

Yeong Hann Ling, Shalini M Krishnan, Christopher T Chan, Henry Diep, Dorota Ferens, Jaye Chin-Dusting, Barbara K Kemp-Harper, Chrishan S Samuel, Timothy D Hewitson, Eicke Latz, Ashley Mansell, Christopher G Sobey, Grant R Drummond,

<h4>Objective</h4>To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension.<h4>Methods</h4>Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal ... Read more >>

Pharmacol Res (Pharmacological research)
[2017, 116:77-86]

Cited: 17 times

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Therapeutic Potential of Nitroxyl (HNO) Donors in the Management of Acute Decompensated Heart Failure.

Barbara K Kemp-Harper, John D Horowitz, Rebecca H Ritchie,

Heart failure (HF) is a major cause of hospital admission in the Western world, yet there remains a paucity of effective pharmacological management options. With the recent development of synthetic, next-generation nitroxyl (HNO) donors and their progress into clinical trials, it is timely to now provide an update on the ... Read more >>

Drugs (Drugs)
[2016, 76(14):1337-1348]

Cited: 14 times

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Adverse vascular remodelling is more sensitive than endothelial dysfunction to hyperglycaemia in diabetic rat mesenteric arteries.

Nicola Kahlberg, Cheng Xue Qin, Jarryd Anthonisz, Edwina Jap, Hooi Hooi Ng, Maria Jelinic, Laura J Parry, Barbara K Kemp-Harper, Rebecca H Ritchie, Chen Huei Leo,

Increased vascular stiffness and reduced endothelial nitric oxide (NO) bioavailability are characteristic of diabetes. Whether these are evident at a more moderate levels of hyperglycaemia has not been investigated. The objectives of this study were to examine the association between the level of glycaemia and resistance vasculature phenotype, incorporating both ... Read more >>

Pharmacol Res (Pharmacological research)
[2016, 111:325-335]

Cited: 12 times

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Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization.

Karen L Andrews, Amanda K Sampson, Jennifer C Irvine, Waled A Shihata, Danielle L Michell, Natalie G Lumsden, Chloe Lim, Olivier Huet, Grant R Drummond, Barbara K Kemp-Harper, Jaye P F Chin-Dusting,

Nitroxyl anion (HNO) donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure. Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leucocyte adhesion to the endothelium and macrophage polarization. Similar to the NO donor glyceryl trinitrate ... Read more >>

Clin Sci (Lond) (Clinical science (London, England : 1979))
[2016, 130(18):1629-1640]

Cited: 10 times

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The Anti-fibrotic Actions of Relaxin Are Mediated Through a NO-sGC-cGMP-Dependent Pathway in Renal Myofibroblasts In Vitro and Enhanced by the NO Donor, Diethylamine NONOate.

Chao Wang, Barbara K Kemp-Harper, Martina Kocan, Sheng Yu Ang, Tim D Hewitson, Chrishan S Samuel,

<h4>Introduction</h4>The anti-fibrotic hormone, relaxin, has been inferred to disrupt transforming growth factor (TGF)-β1/Smad2 phosphorylation (pSmad2) signal transduction and promote collagen-degrading gelatinase activity via a nitric oxide (NO)-dependent pathway. Here, we determined the extent to which NO, soluble guanylate cyclase (sGC) and cyclic guanosine monophosphate (cGMP) were directly involved in the ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2016, 7:91]

Cited: 10 times

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Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance.

Karen L Andrews, Natalie G Lumsden, Julie Farry, Ann-Maree Jefferis, Barbara K Kemp-Harper, Jaye P F Chin-Dusting,

Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO•), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to ... Read more >>

Clin Sci (Lond) (Clinical science (London, England : 1979))
[2015, 129(2):179-187]

Cited: 19 times

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