“Spontaneously” hypertensive mice: A potential genetic model for the study of the relationship between heart size and blood pressure

Elias, Merrill F.; Sorrentino, Rosemary N.; Pentz, Clyde A.; Schlager, Gunther

doi:10.1080/03610737508257964

Cited by 10 publications

(2 citation statements)

References 14 publications

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“…It is not unusual for animals selected for a particular phenotype to exhibit comorbid characteristics remote to the selection criteria (Elias et al, 1975;Sandnabba, 1996;Gonzalez et al, 1998;Ferguson and Kennaway, 1999). In the present investigation, fast rats displayed marked acquisition impairments in a simple fixedposition spatial Morris water-maze, as well as in a test in which the position of the platform was altered after the response was acquired.…”

Section: Discussionmentioning

confidence: 52%

Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity

Anisman

McIntyre

2002

J. Neurosci.

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Rat lines selectively bred for differences in amygdala excitability, manifested by "fast" or "slow" kindling epileptogenesis, display several comorbid features related to anxiety and learning. To assess the nature of the learning deficits in fast kindling rats, performance was evaluated in several variants of a Morris water-maze test. Regardless of whether the location of the platform was fixed or varied over days (matching-to-place task), the fast rats displayed inferior performance, suggesting both working and reference memory impairments. Furthermore, when the position of the platform was altered after the response was acquired, fast rats were more persistent in emitting the previously acquired response. The poor performance of fast rats was also evident in both cued and uncued tasks, indicating that their disturbed learning was not simply a reflection of a spatial deficit. Moreover, fast rats could be easily distracted by irrelevant cues, suggesting that these animals suffered from an attentional disturbance. Interestingly, when rats received several training trials with the platform elevated, permitting them to develop the concept of facile escape, the performance of fast rats improved greatly. The performance disturbance in fast rats may reflect difficulties in forming a conceptual framework under conditions involving some degree of ambiguity, as well as greater distractibility by irrelevant cues. These various attributes of the fast rats may serve as a potentially useful animal model of disorders characterized by an attention deficit.

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Section: Discussionmentioning

confidence: 52%

Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity

Anisman

McIntyre

2002

J. Neurosci.

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“…Despite being hypertensive from a relatively young age, BPH/2 mice do not have greater absolute heart weight nor left ventricle weight compared with normotensive BPN/3 mice (Schlager et al, 1979; Schlager and Sides, 1997). However, the body weight of BPH/2 mice was lower than BPN/3 mice, so when expressed as HW:BW ratio, there was a tendency for this measure to be greater in BPH/2 mice (Schlager and Sides, 1997) and normotensive C57Bl/6 mice (Elias et al, 1975b). Thus, a degree of cardiac hypertrophy is apparent in BPH/2 mice but it appears to be mild.…”

Section: Heart Vessel and Kidney Structure And Functionmentioning

confidence: 99%

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

et al. 2019

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It has been 45 years since Gunther Schlager used a cross breeding program in mice to develop inbred strains with high, normal, and low blood pressure (BPH/2, BPN/3, and BPL/1 respectively). Thus, it is timely to gather together the studies that have characterized and explored the mechanisms associated with the hypertension to take stock of exactly what is known and what remains to be determined. Growing evidence supports the notion that the mechanism of hypertension in BPH/2 mice is predominantly neurogenic with some of the early studies showing aberrant brain noradrenaline levels in BPH/2 compared with BPN/3. Analysis of the adrenal gland using microarray suggested an association with the activity of the sympathetic nervous system. Indeed, in support of this, there is a larger depressor response to ganglion blockade, which reduced blood pressure in BPH/2 mice to the same level as BPN/3 mice. Greater renal tyrosine hydroxylase staining and greater renal noradrenaline levels in BPH/2 mice suggest sympathetic hyperinnervation of the kidney. Renal denervation markedly reduced the blood pressure in BPH/2 but not BPN/3 mice, confirming the importance of renal sympathetic nervous activity contributing to the hypertension. Further, there is an important contribution to the hypertension from miR-181a and renal renin in this strain. BPH/2 mice also display greater neuronal activity of amygdalo-hypothalamic cardiovascular regulatory regions. Lesions of the medial nucleus of the amygdala reduced the hypertension in BPH/2 mice and abolished the strain difference in the effect of ganglion blockade, suggesting a sympathetic mechanism. Further studies suggest that aberrant GABAergic inhibition may play a role since BPH/2 mice have low GABAA receptor δ, α4 and β2 subunit mRNA expression in the hypothalamus, which are predominantly involved in promoting tonic neuronal inhibition. Allopregnanolone, an allosteric modulator of GABAA receptors, which increase the expression of these subunits in the amygdala and hypothalamus, is shown to reduce the hypertension and sympathetic nervous system contribution in BPH/2 mice. Thus far, evidence suggests that BPH/2 mice have aberrant GABAergic inhibition, which drives neuronal overactivity within amygdalo-hypothalamic brain regions. This overactivity is responsible for the greater sympathetic contribution to the hypertension in BPH/2 mice, thus making this an ideal model of neurogenic hypertension.

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Brain catecholamines and organ weight of mice genetically selected for high and low blood pressure

1979

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“Spontaneously” hypertensive mice: A potential genetic model for the study of the relationship between heart size and blood pressure

Cited by 10 publications

References 14 publications

Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity

Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Brain catecholamines and organ weight of mice genetically selected for high and low blood pressure

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