In the past it has been shown, by using tail cuff blood pressure measurements, that intracerebroventricular (icv) injection of the mineralocorticoid antagonist RU28318 decreases blood pressure (BP) and heart rate (HR) after 7 h. Direct BP measurements demonstrated that it was not a decrease in HR and BP but rather the blocking of an increase. After icv injection, the glucocorticoid antagonist RU38486 had the opposite effect on tail cuff BP, after 24 h BP was higher than in control animals. Also, RU28318 has been shown to have anxiolytic-like effects in an elevated plus-maze paradigm.

The aim of this experiment was to gain more insight, with the use of telemetry, into the effects of RU28318 and RU38486, especially to what extent they are induced by the experimental procedure. Wistar rats were equipped with an icv cannula and a TL11M2-C50 PXT ECG/BP transmitter or a TA11ETA-F40-L20 ECG transmitter (Data Sciences International). After a recovery period of at least 10 days the rats were icv injected with RU28318, RU38486 or vehicle. After 1.5, 6.5 and for RU38486 also after 23.5 h the rats were subjected to 32 °C for 30 min, after which they were restrained during 1.5 min and the pressure of the tail cuff was mimicked by slightly pinching the base of the tail. 7 h after icv injection of 100 ng RU28318, the stress-induced increase in HR was reduced by about 50% from 128 bpm (vehicle) to 67 bpm (RU28318) (p=0.0133). 100 ng RU38486 icv increased the stress-induced increase in HR after 24 h from 80 bpm in vehicle treated rats to 123 bpm in RU38486 treated rats (p=0.005). The blood pressure during stress increased from 113 to 129 mmHg (vehicle vs. RU38486, p=0.0187). From the vehicle treated group it became apparent that rats show habituation when restrained 3 times within 24 h (peak HR 496, 420 and 406 bpm and peak BP 121, 112 and 113 mmHg after 2, 7 and 24 h, respectively) It can be concluded that central mineralocorticoid or glucocorticoid receptor blockade has a profound influence on both BP and HR changes during (restraint) stress.