Long-Term Effects of Betamethasone on Blood Pressure and Hypothalamo-Pituitary-Adrenocortical Function in Spontaneously Hypertensive and Normotensive Rats

Abstract

An enhanced hypothalamo-pituitary-adrenocortical (HPA) activity has been described during onset of elevated blood pressure in spontaneously hypertensive rats (SHR). An instability of the HPA axis could thus contribute to the development of hypertension in these animals. Glucocorticoid effects on blood pressure and HPA function were studied therefore in SHR and normotensive Wistar-Kyoto (WKY) and Wistar rats. Beginning at 4 weeks of age, the rats were treated with 0.1 and 0.5 µg betamethasone per milliliter drinking water for 7 weeks. SHR and WKY responded with a significant elevation in average blood pressure. In SHR, mean blood pressure rose from 181.4 ± 3.9 (mean ± SEM) to 203.1 ± 2.8 mm Hg in response to the lower dose of betamethasone and to 209.2 ± 4.0 mm Hg in response to 0.5 µg betamethasone per milliliter drinking water. In WKY, blood pressure increased from 134.4 ± 3.3 to 148.2 ± 3.0 and 157.9 ± 4.5 mm Hg in response to the lower and higher dose of betamethasone, respectively. No significant effect was seen in Wistar rats, where the mean blood pressure values changed insignificantly from 133.8 ± 2.1 to 136.3 ± 3.2 and 135.6 ± 2.4 mm Hg. Stress-induced secretion of corticosterone was significantly suppressed in a dose-dependent manner in all three strains. Stress-induced secretion of adrenocorticotropin was markedly reduced by 0.5 µg betamethasone per milliliter in SHR and by both doses in WKY. No significant effect, however, was seen in Wistar rats. A predisposition to the hypertensiogenic actions of glucocorticoids was found therefore in SHR and WKY, but not in Wistar rats.

Enhancement of Glucocorticoid and Mineralocorticoid Receptor Density in the Microcirculation of the Spontaneously Hypertensive Rat

“…The receptor plays an important role in several physiological processes, including energy homeostasis and modulation of the central nervous system, and has well‐recognized anti‐inflammatory and immunosuppressive activities (2). It plays a negative feedback role in the hypothalamo‐pituitary‐adrenal axis (23), known to be involved in blood pressure regulation of the SHR (17). Enhanced glucocorticoid receptor density is associated with insulin resistance (38).…”

Differential Hypothalamic-pituitary-adrenal Response to Stress among Rat Strains: Methodological Considerations and Relevance for Neuropsychiatric Research

“…Results are also controversial regarding the response to stressors. After ether exposure, the corticosterone response of WKY has been shown to be higher [ 128 ], similar [ 119 ] or lower [ 133 ] compared with SHR. In the latter study, WKY, SHR and outbred Wistar rats were included and lower ACTH and corticosterone responses of both WKY and Wistar versus SHR were found, with similar responses in WKY and Wistar at all ages.…”

Corticotropin Effects on Blood Pressure and Fluid and Electrolyte Homeostasis in Five Strains of Rats

“…This lack of exaggerated response is in keeping with observations that the effects of the synthetic steroid /?-methasone on BP were similar in SHR and WKY. 26 We have previously studied the effects of corticotropin administration in Sprague-Dawley rats 10 and included in this study a postinjection control period in this strain to determine the effects of corticotropin withdrawal. In the sham (saline) injection animals, systolic BP continued to rise postinjection, as did body weight and water intake, whereas urine volume and electrolyte excretion remained relatively constant.…”