| Opioid peptides are involved in the central control of the cardiovascular system. Previously this laboratory demonstrated that the hippocampal kappa-opioid receptor system is dysfunctional in the spontaneous hypertensive rat (SHR). The hippocampus of SHR possessed increased kappa receptor density and lower levels of dynorphin peptide, due to deficient preprodynorphin mRNA expression. The hypertension in this model could be attenuated with kappa-agonists. The insufficient production of hippocampal dynorphins was believed to be an aberration of the genetic SHR model and may not reflect human hypertension. The isolated hypertensive rat (IHR) is a mild emotional stress-induced hypertensive model evoked via short-term isolation. It was the purpose of this research to demonstrate the involvement of the hippocampal kappa receptor phenomenon that is related to hypertension in SHR, in another model of hypertension, the IHR.;Male Sprague Dawley rats exhibited isolation-induced hypertension, which could be prevented via pretreatment with U62, 066E (a non-peptide kappa-opioid receptor agonist). A decrease in hippocampal Dyn A (1--8) peptide was observed in isolated rats, that was accompanied by an increase in apparent hippocampal kappa-opioid receptor number, when compared to grouped rats. Further reduction of kappa-opioid receptor density by hippocampal microinjection of rat kappa-opioid receptor antisense oligodeoxynucleotide, exacerbated isolation-induced hypertension, as did hippocampal administration of norbinaltorphimine (kappa-opioid receptor antagonist). These data implied that the hippocampal kappa-opioid receptor system is not quiescent in the isolated hypertensive rat. In addition, hippocampal colchicine lesions, which allow for selective destruction of the sole dynorphin producing dentate granule cells, also exacerbated hypertension in IHR. These observations exhibit a similar pattern of results with the IHR, previously observed with the SHR. The endogenous hippocampal kappa-opioid system may be activated to reverse or prevent isolation-induced hypertension, and further disruption of this system may exacerbate hypertension.;In conclusion, these studies implicate the involvement of the kappa-opioid receptor system in the pathophysiology of isolation-induced hypertension, and are an important contribution to the validity of the IHR, which may be a valuable model for screening anti-hypertensive drugs. These data supply increased evidence for the neural role of the hippocampal system in the restraint of blood pressure in more than one model of hypertension, and provides potential for development of novel therapeutic agents that may act upon the central nervous system to prevent and/or treat hypertension. |
