Hippocampal administration of kappa-opioid receptor antisense exacerbates isolation-induced hypertension

Isolation of young male Sprague Dawley rats for 7 days provoked hypertension which was exacerbated by hippocampal administration of an antisense oligodeoxynucleotide targeted to the kappa-opioid receptor (1 microg/0.5 microL bilaterally, twice daily, during the isolation or grouping period). Systolic blood pressure rose from a mean of 134 to 162 mmHg in isolated rats treated with antisense and only 139 to 151 mmHg in grouped rats treated with antisense. In grouped rats treated with either vehicle or missense, isolation caused a mean increase in systolic blood pressure of only 16 and 14 mmHg respectively. Neither the missense oligodeoxynucleotide nor the vehicle had any significant effects upon systolic pressure in grouped rats, which had not been isolated. Pharmacological studies indicated that rats previously treated with the antisense had no significant depressor response to U62, 066E (a non-peptide kappa agonist known to reduce blood pressure acutely when administered into the hippocampus), however rats previously treated with vehicle or missense exhibited a significant hypotensive response to the drug. This implies that the antisense had reduced the density or activity of the kappa receptors within the hippocampal formation. These data are in accordance with our previous studies, i.e. in several rat models of hypertension, the increase in blood pressure may be modulated via hippocampal kappa opioid receptors.