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 nM para-iodoclonidine (125I-PIC) revealed that binding was equally and concentration-dependently inhibited by epinephrine and imidazole-4-acetic acid (IAA), implying 125I-PIC binding to cardiac alpha2-adrenergic and I1-receptors, respectively. After irreversible blockade of alpha2-adrenergic receptors, binding was inhibited by the selective I1-agonist, moxonidine, and the I1-antagonist, efaroxan, in a concentration-dependent (10-12 to 10-5 M) 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.