Imidazoline Receptors but Not α2-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

We have recently identified imidazoline I 1 -receptors in the heart. In the present study, we tested regulation of cardiac I 1 -receptors versus α 2 -adrenoceptors in response to hypertension and to chronic exposure to agonist. Spontaneously hypertensive rats (SHR, 12–14 weeks old) received moxonidine (10, 60, and 120 μg/kg/h s.c.) for 1 and 4 weeks. Autoradiographic binding of 125 I-paraiodoclonidine (0.5 nM, 1 h, 22°C) and inhibition of binding with epinephrine (10 –10 –10 –5 M) demonstrated the presence of α 2 -adrenoceptors in heart atria and ventricles. Immunoblotting and reverse transcription-polymerase chain reaction identified α 2A -α 2B -, and α 2C , and -adrenoceptor proteins and mRNA, respectively. However, compared with normotensive controls, cardiac α 2 -adrenoceptor kinetic parameters, receptor proteins, and mRNAs were not altered in SHR with or without moxonidine treatment. In contrast, autoradiography showed that up-regulated atrial I 1 -receptors in SHR are dose-dependently normalized by 1 week, with no additional effect after 4 weeks of treatment. Moxonidine (120 μg/kg/h) decreased B max in right (40.0 ± 2.9–7.0 ± 0.6 fmol/unit area; p p p p B max only correlated with the 85-kDa protein ( R 2 = 0.57; p 2 -receptors. The weak but significant correlation between the two imidazoline receptor proteins ( R 2 = 0.28; p 1 -receptors and α 2 -adrenoceptors, but only I 1 -receptors are responsive to hypertension and to chronic in vivo treatment with a selective I 1 -receptor agonist.