Chronic kappa-opioid receptor antagonism delays the rise in blood pressure in spontaneously hypertensive rats.

A 4-week subcutaneous treatment with the kappa-opioid receptor antagonists, MR 2266 or MR 1452, delayed the age-dependent increase in systolic blood pressure in young spontaneously hypertensive rats (SHR), but not in normotensive rats. The content of beta-endorphin, [Leu5]enkephalin, and catecholamines in various brain tissues was not affected by MR 2266. Specificity of the kappa-opioid receptor antagonism was tested in SHR by injection of the kappa-opioid agonist, MR 2033, and the mu agonist, morphiceptin, after 28 days of MR 1452 or saline and 2 days after the end of treatment. The increase in mean arterial blood pressure (MAP) after MR 2033 did not differ between the two groups at the 28th day of treatment but was higher 2 days later in the previous MR 1452 group, possibly indicating up-regulation of kappa-opioid receptors. Morphiceptin did not alter MAP during or after MR 1452. It is concluded that kappa-opioid receptors may have a tonic influence on the age-dependent increase of blood pressure in SHR but not in normotensive rats.