Spontaneously Hypertensive Rats

Abstract

Abstract-Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se. (Hypertension. 1998;31:968-972.)Key Words: rats, inbred SHR Ⅲ learning Ⅲ memory Ⅲ aging Ⅲ pharmacology Ⅲ models A great expansion of experimental research began with the development of rat strains with genetically inherited hypertension. The SHR offers specific and uniform genetic predisposition, 1 thus allowing the study of the causes, mechanisms, and pathology of hypertension, as well as its behavioral consequences, and the comparison of the efficacy of proposed therapeutic interventions in relation to existing clinical treatments. Moreover, central neurohormonal mechanisms constitute the dominating trigger influence in SHR 1 and provide a model of hypertension that allows the study of the combined influence of both aging and hypertension on cognitive and physical functions on different developmental stages.2,3 Notwithstanding, the SHR is a genetic model, and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to the elevated blood pressure per se. Normal aging also produces a slow decline in neuron population, tissue distensibility, basal metabolic rate, and oxygen consumption, thus affecting cardiovascular performance. The aim of the present work was to present evidence obtained in our laboratory supporting the idea that the SHR is a suitable behavioral model to test drugs with potential therapeutic us...

Chronic, Severe Hypertension Does Not Impair Spatial Learning and Memory in Sprague-Dawley Rats

“…Further, we have demonstrated that chronic antihypertensive treatment of SHR nearly normalizes memory in the 12-mo-old SHR. Similar deficits in SHR have recently been demonstrated by other researchers using similar tasks (Meneses et al 1996;Gattu et al 1997a,b;Meneses and Hong 1998b). Learning deficits have also been reported in other hypertensive rodent models of hypertension, including genetic (e.g., Hirawaet al 1999) and induced (e.g., Meyer et al 1998) models.…”

“…Much of the impetus for this study arises from our earlier findings that at 12 mo of age, SHR display a significant impairment of learning and memory and that this deficit is prevented by continuous antihypertensive therapy with an angiotensin-converting enzyme inhibitor (Wyss et al 1992; see also Gattu et al 1997a,b;Meneses and Hong 1998b). Further, compared with young SHR, 26-50-wk-old SHR are very impaired in performing a learned escape response (Hecht et al 1978).…”

“…Such animal models (e.g., Meneses and Hong 1998a) are important for defining the contribution of hypertension to memory impairments and for assessing the ability of antihypertensive drugs to improve or worsen the memory deficits in hypertensive individuals (e.g., Prince et al 1996;Meneses and Hong 1998b). Several studies suggest that various antihypertensive drugs affect memory and learning (Lasser et al 1989;Bulpitt and Fletcher 1992;Wyss and Van Groen 1994).…”

L-Type Voltage-Dependent Calcium Channel Antagonists Impair Perirhinal Long-Term Recognition Memory and Plasticity Processes

“…It is important to appreciate that the effects of L-type VDCC antagonism on memory appear to be dependent on the dose regimen: chronically repeated low doses have been reported to have, if any, beneficial effects on memory (Disterhoft et al, 1996;Batuecas et al, 1998;Meneses and Hong, 1998;Kane and Robinson, 1999;Veng et al, 2003;Lashgari et al, 2006)-although these might be indirect, because of improved cardiac performance. Thus, the amnesic effects of single acute doses in rats should not be taken as directly relevant to the chronic treatment of human cardiovascular problems.…”

Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks

“…26 Furthermore, the time course of changes does not fit with an MCAo-unrelated spontaneous decline as the day 28 score showed significant recovery relative to previous time point. Nevertheless, SHRs do develop histopathologic and behavioral stigmata of accelerated brain aging over time, 21,35 which could have contributed to the behavioral effects of MCAo by reducing the brain reserve. …”