Imidazoline Receptors in the Heart: Characterization, Distribution, and Regulation

Imidazoline receptors were identified in cardiac tissues of various species. Imidazoline receptors were immunolocalized in the rat heart. Membrane binding and autoradiography on frozen heart sections using 0.5 n M para-iodoclonidine (I-PIC) revealed that binding was equally and concentration-dependently inhibited by epinephrine and imidazole-4-acetic acid (IAA), implying I-PIC binding to cardiac α2-adrenergic and I1-receptors, respectively. After irreversible blockade of α2-adrenergic receptors, binding was inhibited by the selective I1-agonist, moxonidine, and the I1-antagonist, efaroxan, in a concentration-dependent (10 to 10M) manner. Calculation of kinetic parameters revealed that in canine left and right atria, I1-receptor Bmax was 13.4 ± 1.7 and 20.1 ± 3.0 fmol/mg protein, respectively. Compared to age-matched normotensive Wistar Kyoto rats, I1-receptors were increased in 12-week-old hypertensive rat (SHR) right (22.6 ± 0.3 to 43.7 ± 4.4 fmol/unit area, p < 0.01) and left atria (13.3 ± 0.6 to 30.2 ± 4.1 fmol/unit area, p < 0.01). Also, compared to corresponding normal controls, Bmax was increased in hearts of hamsters with advanced cardiomyopathy (13.9 ± 0.4 to. 26.0 ± 2.3 fmol/unit area, p < 0.01) and in human ventricles with heart failure (12.6 ± 1.3 to 35.5 ± 2.9 fmol/mg protein, p < 0.003). These studies demonstrate that the heart possesses imidazoline I1-receptors that are up-regulated in the presence of hypertension or heart failure, which would suggest their involvement in cardiovascular regulation.