Increased Number of Cardiac Adrenergic Receptors Following Local Heart Irradiation

Abstract

The effect of local X irradiation on cardiac alpha and beta receptors was studied in Wistar rats. Animals were given local heart irradiation with single doses of 15 or 20 Gy and were examined after a range of latency times of 7 to 400 days. Using the radioactive ligands [3H]CGP-12177 and [3H]prazosin, the maximal binding capacity was determined from saturation experiments. At 7 days after 20 Gy the maximal binding capacity of both alpha and beta receptors was reduced to below the level of untreated control animals. Subsequently it rose continually to a maximum of 160% of the control level for beta receptors and 130% for alpha receptors at 400 days postirradiation. The antagonist affinity as judged from the dissociation constant for [3H]CGP 12177 and [3H]prazosin did not change significantly. A similar effect was observed after 15 Gy. An increase in adrenergic receptors may represent an important pathogenetic link between early morphological and late functional changes in the pathogenesis of radiation-induced heart disease.

Demonstration of the suitability of CGP 12177 for in vivo studies of β‐adrenoceptors

“…If it is assumed that there are 100 mg protein per gram of wet tissue, values for Bma, become 440 fmol mg-' protein for lung and -60 fmol mg-' for heart. The Bma, of 60 fmol mg-' is within the range of values (12-70 fmol mg-') determined with [3H]-CGP 12177 in rat cardiac membranes or myocytes in vitro (Limas & Limas, 1987;Shepherd et al, 1987;Lauk et al, 1989;Steinkraus et al, 1989;Tsuchihahsi et al, 1989;Mauz & Pelzer, 1990;Reithmann et al, 1990;Rocha-Singh et al, 1991). Although the regional variations were not significant the results are in agreement with autoradiographic studies using lipophilic ligands such as ['251I]-iodocyanopindolol which indicate that the number of B-adrenoceptors is greatest in the atrial walls .…”

Chlorisondamine, a sympathetic ganglionic blocker, moderates the effects of whole-body irradiation (WBI) on early host defense to a live bacterial challenge

“…However, in the context of cardiovascular disease, there have been multiple reports that higher, clinically relevant doses of radiation can alter adrenergic receptor density and myocardia NE concentrations [49][50][51][52][53]. Therefore, it is feasible that nerve loss in immune organs could disrupt sympathetic activity.…”

Late Effects in Mouse Heart after60Co γ-irradiation of the Brain: An Ultrastructural Study

“…1976, 1978, Stearner et al . 1979, Yang and Ainsworth 1982, Stewart and Fajardo 1984, Lauk et al 1989) . However, the indirect effect of radiation on this organ has not been investigated .…”