Resistance to myocardial ischemia in five rat strains:  is there a genetic component of cardioprotection?

There is a need to develop new and more consistent animal models of cardioprotection. Traditionally, outbred dogs, rabbits, and rats have been studied. We determined resistance to ischemia in isolated hearts from inbred strains of rats. Hearts from inbred rats: SS/Mcw (Dahl S, Dahl salt-sensitive), DA/Hsd (Dark Agouti), LEW/Hsd (Lewis), and BN/SsN/Mcw (Brown Norway); and from an outbred rat: Hsd:WIST (Wistar) were subjected to 27 min of global, no-flow ischemia, followed by 3 h of reperfusion. Infarct size in the Brown Norway rat was 2.5 times less than that observed in the Dahl S rat, with the Dark Agouti, Lewis, and Wistar rats intermediate in response. Hearts from Brown Norway rats were also most resistant to ischemia in terms of postischemic enzyme leakage and contractile and vascular function compared with other strains. The average polymorphism rate between strains revealed that such strains were genetically diverse. This study demonstrates strain differences in resistance to myocardial ischemia, suggesting these rats could be used to study a genetic and/or environmental basis for these differences and to provide new animal models for the physiological study of cardioprotection.

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PPARγ-Independent Side Effects of Thiazolidinediones on Mitochondrial Redox State in Rat Isolated Hearts

Cells ◽

10.3390/cells9010252 ◽

2020 ◽

Vol 9 (1) ◽

pp. 252 ◽

Cited By ~ 1

Author(s):

Matthias L. Riess ◽

Reem Elorbany ◽

Dorothee Weihrauch ◽

David F. Stowe ◽

Amadou K.S. Camara

Keyword(s):

Redox State ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Brown Norway ◽

Mitochondrial Uncoupling ◽

Norway Rat ◽

Isolated Hearts ◽

Mitochondrial Redox State ◽

Pparγ Agonists ◽

Brown Norway Rat

The effect of anti-diabetic thiazolidinediones (TZDs) on contributing to heart failure and cardiac ischemia/reperfusion (IR) injury is controversial. In this study we investigated the effect of select TZDs on myocardial and mitochondrial function in Brown Norway rat isolated hearts. In a first set of experiments, the TZD rosiglitazone was given acutely before global myocardial IR, and pre- and post-IR function and infarct size were assessed. In a second set of experiments, different concentrations of rosiglitazone and pioglitazone were administered in the presence or absence of the specific PPARγ antagonist GW9662, and their effects on the mitochondrial redox state were measured by online NADH and FAD autofluorescence. The administration of rosiglitazone did not significantly affect myocardial function except for transiently increasing coronary flow, but it increased IR injury compared to the control hearts. Both TZDs resulted in dose-dependent, reversible increases in mitochondrial oxidation which was not attenuated by GW9662. Taken together, these data suggest that TZDs cause excessive mitochondrial uncoupling by a PPARγ-independent mechanism. Acute rosiglitazone administration before IR was associated with enhanced cardiac injury. If translated clinically, susceptible patients on PPARγ agonists may experience enhanced myocardial IR injury by mitochondrial dysfunction.

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Brown Norway Rat Asthma Model of Diphenylmethane 4,4′-Diisocyanate

Inhalation Toxicology ◽

10.1080/08958370500224631 ◽

2005 ◽

Vol 17 (13) ◽

pp. 729-739 ◽

Cited By ~ 18

Author(s):

Jürgen Pauluhn

Keyword(s):

Brown Norway ◽

Norway Rat ◽

Asthma Model ◽

Brown Norway Rat

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Knockdown of Add3 impairs the myogenic response of renal afferent arterioles and middle cerebral arteries

AJP Renal Physiology ◽

10.1152/ajprenal.00529.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. F971-F981 ◽

Cited By ~ 18

Author(s):

Fan Fan ◽

Mallikarjuna R. Pabbidi ◽

Ying Ge ◽

Longyang Li ◽

Shaoxun Wang ◽

...

Keyword(s):

Vascular Reactivity ◽

Vascular Dysfunction ◽

Cerebral Arteries ◽

Chromosome 1 ◽

Brown Norway ◽

Myogenic Response ◽

Norway Rat ◽

Vasoconstrictor Response ◽

Brown Norway Rat ◽

Interfering Rna

We have reported that the myogenic response of the renal afferent arteriole (Af-art) and middle cerebral artery (MCA) and autoregulation of renal and cerebral blood flow are impaired in Fawn-Hooded Hypertensive (FHH) rats. Transfer of a region of chromosome 1 containing γ-adducin (Add3) from the Brown Norway rat rescued the vascular dysfunction and the development of renal disease. To examine whether Add3 is a viable candidate gene altering renal and cerebral hemodynamics in FHH rats, we knocked down the expression of Add3 in rat Af-arts and MCAs cultured for 36-h using a 27-mer Dicer-substrate short interfering RNA (DsiRNA). Control Af-arts constricted by 10 ± 1% in response to an elevation in pressure from 60 to 120 mmHg but dilated by 4 ± 3% when treated with Add3 DsiRNA. Add3 DsiRNA had no effect on the vasoconstrictor response of the Af-art to norepinephrine (10−7 M). Add3 DsiRNA had a similar effect on the attenuation of the myogenic response in the MCA. Peak potassium currents were threefold higher in smooth muscle cells isolated from Af-arts or MCAs transfected with Add3 DsiRNA than in nontransfected cells isolated from the same vessels. This is the first study demonstrating that Add3 plays a role in the regulation of potassium channel function and vascular reactivity. It supports the hypothesis that sequence variants in Add3, which we previously identified in FHH rats, may play a causal role in the impaired myogenic response and autoregulation in the renal and cerebral circulation.

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