Prevention of isolation-induced hypertension by intrahippocampal administration of a nonpeptide kappa-opioid receptor agonist.

Previous research in this laboratory showed that hypertension in the spontaneous hypertensive rat (SHR) appears to correlate to insufficient production of hippocampal dynorphins, and that blood pressure could be reduced by intrahippocampal administration of dynorphins and nonpeptide kappa agonists. The purpose of the present study was to investigate whether kappa agonists could prevent the development of hypertension in a different hypertensive model, i.e., the isolated male rat model of hypertension (IHR). Isolation of young male rats for 5-7 days in standard rat cages caused an increase in systolic blood pressure from a mean of 132 to 184 mmHg. The blood pressures of rats grouped 3 per cage remained stable. Rats received the nonpeptide kappa agonist U62, 066E, (Spiradoline, Upjohn), 10 nmoles/0.2 microl or drug vehicle bilaterally into the the hippocampus for 3 days prior to and during isolation or grouping. Animals treated with U62, 066E did not develop hypertension as compared to isolated animals treated with vehicle. The isolation procedure used in these studies appears to induce anxietal stress, as indicated by reduced time spent by the rats in the open arms of the elevated-plus maze. This time is increased by U62, 066E, suggesting that the drug possesses anxiolytic properties and may reduce hypertension in part, by blocking an anxiety/stress component. These data strengthen our previous findings that opioids in the hippocampus may be important in restraining increased blood pressure provoked by environmental stimuli such as isolation.