The binding of [3H]
idazoxan in the presence of l-
epinephrine was used to characterize and quantitate
imidazoline receptors in the brain of spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats before and after chronic
imidazoline drug treatment. In the cerebral cortex of WKY and SHR rats, the rank order of potency of imidazoli(di)ne drugs (
cirazoline greater than
idazoxan greater than
naphazoline greater than
clonidine much greater than
RX821002) competing with [3H]
idazoxan showed the specificity for an
imidazoline receptor which also appeared heterogeneous in nature. In SHR rats, the density of
imidazoline receptors (hypothalamus greater than medulla oblongata greater than cerebral cortex) and proportion of high- and low-affinity sites for the receptor were not different from those in WKY and SD rats, suggesting that the receptor itself is not altered in
hypertension. However, chronic treatment with
idazoxan and
cirazoline (10 and 1 mg/kg, i.p., every 12 h for 7 days) consistently increased (about 35%) the density of
imidazoline receptors in the brain of WKY and SD, but not in SHR rats. A similar treatment with
RX821002, the 2-methoxy analog of
idazoxan, which is a highly selective alpha-2
adrenoceptor antagonist, did not increase the density of brain
imidazoline receptors. Moreover, the up-regulation of these receptors induced by
cirazoline was still present after alkylation of the alpha-2
adrenoceptors with
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. The lack of regulation by
idazoxan and
cirazoline of the density of
imidazoline receptors in the brain of SHR rats suggests the existence of a relevant abnormality in the adaptive process of these receptors in this genetic model of
hypertension.