Comparison of cardiovascular responses to intrahippocampal μ, δ and κ opioid agonists in spontaneously hypertensive rats and isolation-induced hypertensive rats

Abstract

To investigate the cardiovascular effects of microinjection into the hippocampus of selective mu, delta and kappa opioid receptor agonists in anesthetized spontaneously hypertensive rats, isolation-induced hypertensive rats and their normotensive Wistar-Kyoto and group-housed Sprague-Dawley controls. The microinjection of a selective kappa agonist, spiradoline mesylate, (+/-)-(5alpha, 7alpha, 8beta)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro++ +[4.5]dec-8-yl]-benzeneacetamide mesylate) (5 nmol) into the dorsal region of hippocampus, where injection of control saline failed to affect cardiovascular activities, induced centrally mediated decreases in mean blood pressure and heart rate in both hypertensive and normotensive rats. The effects were blocked by prior treatment of the hippocampus with nor-binaltorphimine dihydrochloride, a selective kappa opioid receptor antagonist The hypotensive and bradycardic effects were quantitatively similar between spontaneously hypertensive rats and Wistar-Kyoto rats and between isolated hypertensive rats and normotensive group-housed rats. The sequential administration of increasing doses (5, 10, 50 nmol) of the selective mu agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin and delta agonists [D-Ala2, D-Leu5]-enkephalin or [D-Pen2, D-Pen5]-enkephalin into the same areas of the hippocampus as used for the kappa agonist had no significant effects on mean blood pressure and heart rate in either hypertensive or normotensive rats. The present results extend our previous findings of a hippocampally mediated hypotensive effect of kappa agonists in the spontaneously hypertensive rat to the isolated rat model of hypertension and they establish that mu and delta opioid receptor agonists similarly applied are ineffective. Hippocampal kappa receptors may have a greater role in cardiovascular control than mu and delta receptors.