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

Abstract

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.

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

“…Compared to age-matched normotensive Wistar Kyoto rats, I 1 -receptor Bmax was 2-fold (P < 0.01) higher in 12-week-old SHR right and left atria, but not altered in ventricles. Compared to corresponding normal controls, Bmax was 2-fold higher (P < 0.01) in ventricles of hamsters with advanced cardiomyopathy and in human ventricles with heart failure ( Figure 1) (15). We also demonstrated that cardiac I 1 -receptors, but not α2-adrenoceptors, are regulated by chronic in vivo exposure to the I 1 -receptor selective ligand, moxonidine.…”

“…Moxonidine (120 µg kg -1 h -1 ) decreased (P < 0.01) I 1 -receptor Bmax in right and left atria to normal levels (Figure 2), without altering α2-adrenoceptor Bmax. These results showed for the first time that imidazoline I 1 -receptors and α2-adrenoceptors are present in heart atria and ventricles, and that only imidazoline I 1 -receptors are responsive to changes in the cardiovascular environment and to chronic exposure to the I 1 -selective agonist, moxonidine (15,16). These results implicate heart imidazoline I 1 -receptors in cardiovascular regulation.…”

“…After irreversible blockade of α2-adrenoceptors, 125 I-PIC binding to heart frozen sections and atrial and ventricular membranes was competitively inhibited by increasing concentrations (10 -12 to 10 -6 M) of moxonidine, but not by epinephrine, implying specific imidazoline I 1 -receptor binding. Data from membrane binding and autoradiography were confirmed by immunohistochemistry and Western blotting (15).…”

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

“…I 1 -receptors are mainly found in the brainstem, adrenal chromaffin cells, and kidneys. In addition, we have recently identified I 1 -receptors in heart atria and ventricles and shown that atrial I 1 -receptors are up-regulated in rat hypertension and ventricular I 1 -receptors are up-regulated in human and hamster heart failure (El-Ayoubi et al, 2002a). In other studies, we demonstrated that acute injections of moxonidine, an imidazoline compound that shows 40 times higher affinity to I 1 -receptor versus ␣ 2 -adrenoceptors, are associated with enhanced release of atrial natriuretic peptide (Mukaddam-Daher and Gutkowska, 2000), a cardiac hormone involved in pressure and volume homeostasis.…”

Imidazole-induced contractility of vascular smooth muscle cells in the presence of U-73122, ODQ, indomethacin and 7-nitroindazole

“…Imidazoline receptors were identified in the pancreas, central nervous system (CNS), kidneys and heart (El-Ayoubi et al 2002, Narahashi 2000. Two subtypes of imidazoline receptors were found: I 1 (controls the central regulation of blood pressure) and I 2 (has neuroprotective function for cerebral ischemia (Greney et al 2000, Nicolic et al 2009).…”