(+)-[H-3]isradipine and [H-3]glyburide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertension

We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel lig and, (+)-[H-3]isradipine (PN200-110), and that of an ATP-sensitive K+ (K-AT P) channel ligand, [H-3]glyburide, to heart, lung and brain membranes isola ted from Sprague-Dawley rats made pulmonary hypertensive by monocrotaline, a pyrrolizidine alkaloid. A single subcutaneous injection of monocrotaline increased right ventricular systolic pressure, a measure of pulmonary arter ial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[H-3]PN200-110 and [H-3]glyburide binding site densities ( B-max) were reduced in hypertrophied right ventricles when normalized per u nit protein in comparison with those of age-matched control (sham) rats, wh ereas the values of the dissociation constant (K-d) of both ligands bound t o the hypertrophied right ventricle were not significantly changed. The [H- 3]PN200-110 binding to the lung membranes of the monocrotaline-induced pulm onary hypertensive rats was increased, The results indicate that the change in the binding of 1,4-dihydropyridine Ca2+ and K-ATP channel ligands to he art membranes may contribute to the pathological alteration of cardiopulmon ary structure and functions in rats with pulmonary hypertension induced by monocrotaline.