Animal models for the study of arterial hypertension

Dornas, Waleska Claudia Amaral; Silva, Marcelo Eustáquio

doi:10.1007/s12038-011-9097-y

Cited by 126 publications

(66 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The basic science evidence demonstrating the effect of hypertension on acute stroke therapies would be strengthened if validated in models other than the SHR. 25,26 …”

Section: Effects Of Different Therapiesmentioning

confidence: 99%

Hypertension and Experimental Stroke Therapies

O’Collins

Donnan

Macleod

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. Methods: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978-2010). Data were combined using meta-analysis and meta-regression, partitioned on the basis of hypertension, stroke model, and therapy. Results: Hypertensive animals were used in 10% of experiments testing 502 therapies. Hypertension was associated with lower treatment efficacy, especially in larger infarcts. Overall, anti-hypertensives did not provide greater benefit than other drugs, although benefits were evident in hypertensive animals even when given after stroke onset. Fifty-eight therapies were tested in both normotensive and hypertensive animals: some demonstrated superior efficacy in hypertensive animals (hypothermia) while others worked better in normotensive animals (tissue plasminogen activator, anesthetic agents). Discussion: Hypertension has a significant effect on the efficacy of candidate stroke drugs: standard basic science testing may overestimate the efficacy which could be reasonably expected from certain therapies and for hypertensive patients with large or temporary occlusions. Keywords: acute stroke; animal models; brain ischemia; hypertension; neuroprotection INTRODUCTION Hypertension-the elevation of blood pressure-dramatically increases the risk of stroke, with an estimated 52% of all strokes attributable to hypertension. 1 Hypertension can be controlled and numerous interventions are used in the longterm management of hypertension to prevent both first-time strokes and their recurrence. 2 Less well understood is how to tackle high blood pressure within the first 24 to 48 hours after stroke and how the presence of hypertension affects the efficacy of neuroprotective treatments administered within this period. Lowering blood pressure is not without risks, and it is generally recommended that blood pressure only be lowered if extreme; nevertheless, there is no consensus on the optimal blood pressure thresholds to trigger initiation of treatment, rates of reduction and blood pressure targets, or how hypertension should be managed with concurrent therapies such as tissue plasminogen activator. [2][3][4] Clinical trials are ongoing. 5 By examining hypertension and anti-hypertensive treatments in experimental (animal) stroke models, we may develop a better understanding of how to manage hypertension in the acute stroke setting. Knowledge of hypertension in basic science is also important in its own right. The external validity of animal testing depends upon the ability to generalize to the clinical setting: it has been a frequent criticism of preclinical drug testing that the paradigm has failed to capture the impact of important comorbidit...

show abstract

“…The basic science evidence demonstrating the effect of hypertension on acute stroke therapies would be strengthened if validated in models other than the SHR. 25,26 …”

Section: Effects Of Different Therapiesmentioning

confidence: 99%

Hypertension and Experimental Stroke Therapies

O’Collins

Donnan

Macleod

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…The environmental factor of high salt intake is extensively involved in the development of essential hypertension, as in many genetic models of hypertension [2]. In Dahl salt-sensitive (S) rats, high salt intake induces inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) with the increase in blood pressure or sympathetic activity [3,4].…”

Section: Introductionmentioning

confidence: 99%

NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1

Shi

et al. 2015

Cardiovasc Toxicol

View full text Add to dashboard Cite

High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1β and attenuating p-IKKβ, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump. The mean arterial pressure and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of p-IKKβ, NF-κB p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1β, and lower levels of IL-10 in the PVN than normal diet rats. Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These findings suggest that high-salt-induced NF-κB activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1β and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates NLRP3, IL-1β and oxidative stress in the PVN and thereby attenuates hypertension.

show abstract

“…This demonstrates the involvement of the ANS. Considering that SHR are animals with increased sympathetic activity [25], treatment with L -NAME will further activate the sympathetic system [26]. Indeed, in this group, we obtained the highest number of exclusively positive correlations between HT and RC, which were drastically reduced and changed to a negative direction after the sympathetic blockade with propranolol (table 2).…”

Section: Discussionmentioning

confidence: 80%

Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Prieto¹,

Villarejo²,

Segarra³

et al. 2014

Neuroendocrinology

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis and the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto and spontaneously hypertensive rats, treated or not treated with L-NAME [N(G)-nitro-L-arginine methyl ester]. This compound not only inhibits the formation of nitric oxide but also disrupts the normal function of the ANS activating the sympathetic nervous system (SNS) to increase BP. In addition, to assess the influence of the SNS, we studied the effect of its blockade by treatment of both strains with propranolol. The present results support the notion that RAS function of the brain-heart-kidney axis, as reflected by the activities of angiotensinases, is reciprocally connected by afferent and efferent mechanisms between these locations, presumably through the ANS. These results reveal new aspects of neuroendocrine regulation possibly involving the ANS.

show abstract

Animal models for the study of arterial hypertension

Cited by 126 publications

References 60 publications

Hypertension and Experimental Stroke Therapies

Hypertension and Experimental Stroke Therapies

NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1

Brain, Heart and Kidney Correlate for the Control of Blood Pressure and Water Balance: Role of Angiotensinases

Contact Info

Product

Resources

About