Open Access(+)-(3H)Isradipine and (3H)Glyburide Bindings to Heart and Lung Membranes From Rats With Monocrotaline-Induced Pulmonary Hypertension.
Author(s) -
Koichi Nakayama,
Yoshihisa Fukuta,
Akihiko Kiyoshi,
Yoshiyuki Iwatsuki,
Kunio Ishii,
Tomohisa Ishikawa,
Mari Iida,
Hijiri Iwata,
Makoto Enomoto
Publication year - 1999
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.81.176
Subject(s) - isradipine , ventricle , pulmonary hypertension , ventricular pressure , lung , medicine , dihydropyridine , chemistry , cardiology , anesthesia , endocrinology , blood pressure , calcium
We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel ligand, (+)-[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (K(ATP)) channel ligand, [3H]glyburide, to heart, lung and brain membranes isolated 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 arterial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[3H]PN200-110 and [3H]glyburide binding site densities (Bmax) were reduced in hypertrophied right ventricles when normalized per unit protein in comparison with those of age-matched control (sham) rats, whereas the values of the dissociation constant (Kd) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [3H]PN200-110 binding to the lung membranes of the monocrotaline-induced pulmonary hypertensive rats was increased. The results indicate that the change in the binding of 1,4-dihydropyridine Ca2+ and K(ATP) channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.