Neuroendocrine or behavioral effects of acute or chronic emotional stress in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.

OBJECTIVE: Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY) strain represent an animal model of human essential hypertension. This strain of rats is known by excessive neuroendocrine and cardiovascular responses under stress. The aim of the present study was: 1. To compare the reactivity of hypothalamic-pituitary-adrenocortical axis (HPA) to acute mild stress of handling between SHR and WKY rats, 2. to compare the behavioral activity of both strains under basal conditions and during chronic unpredictable emotional stress.

METHODS: Seven to eight weeks old male SHR and WKY rats bred in the Physiological Institute, Academy of Sciences of the Czech Republic (Prague) were used. Acute stress was induced by 2-minute handling of the animals in their cage. Blood plasma was analyzed for ACTH and corticosterone (CORT) by specific radioimmunoassay. Chronic unpredictable stress lasted 20 days and consisted of random exposures to following interventions: Light on or off for 24 h, overcrowding i.e. pooling the rats from two cages into one (size 24 x 39 x 23 cm) for 24 h, isolation by placing a single rat into one cage for 24 h, new hierarchy by mixing 4 rats from two different cages for 24 h, limited access to food or water for 1 hour in one day between 3 and 6 p.m., inescapable foot shock (20 shocks, duration 5 s, intensity 10 mA, intershock interval 30 s), tilting the cages for 24 h. The sequence of individual stress exposures was the same in all rats. On day 6, 10 and 20, behavioral activity was measured using the elevated plus-maze in non-stressed control and stressed rats. The results were evaluated by non parametrical Kruskal-Wallis test followed by Mann-Whitney U-test.

RESULTS: The two-minute handling resulted in a significantly higher activation of HPA in the SHR than in the WKY rats (plasma ACTH: 350 +/- 65 pg/ml for SHR vs. 97 +/- 17 pg/ml for WKY p<0.01; plasma corticosterone: 2.8 +/- 1.4 mg/100 ml for SHR vs. 0.7 +/- 0.06 mg/100 ml for WKY p<0.05). In WKY rats no activation of HPA was observed. Elevated plus-maze anxiety test showed inverse behavioral pattern between SHR and WKY rats. In the first test of anxiety the number of open arm entries (OAE) as well as total mobility expressed as total arm entries of the SHR was lower than of the WKY rats (p<0.01) without any difference between stressed and non-stressed animals in either strain. It was gradually increasing in stressed and non-stressed SHR in subsequent sessions markedly exceeding the activity of WKY rats (p<0.01). Stressed WKY rats showed less OAE and total mobility than their controls (p<0.01).

CONCLUSIONS: Our results show enhanced neuroendocrine response to acute handling and enhanced anxiety in acute novelty stress in SHR comparing to WKY rats which suggests a common mechanisms for neuroendocrine and behavioral changes. These results further underline the lack of anxiety related behavior of SHR under chronic emotional stress.