RT Journal Article
SR Electronic
T1 Effects of Propranolol on Bone Metabolism in Spontaneously Hypertensive Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 99
OP 105
DO 10.1124/jpet.110.167643
VO 334
IS 1
A1 Takuma Sato
A1 Michitsugu Arai
A1 Shigemi Goto
A1 Akifumi Togari
YR 2010
UL http://jpet.aspetjournals.org/content/334/1/99.abstract
AB The effects of propranolol (PRO), a nonselective β-adrenergic receptor (β-AR) antagonist with membrane-stabilizing action on bone metabolism, were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. Treatment of SHR with PRO at 1 and 5 mg/kg p.o. for 12 weeks increased bone mass of the lumbar vertebra and proximal tibia without affecting blood pressure, but PRO at 50 and 100 mg/kg with hypotensive action did not increase bone mass. Next, the effects of PRO at 0.1, 1, and 10 mg/kg on bone status were examined in more detail. Compared with the SHR control, not only bone mass but also biomechanical parameters of strength and toughness of the lumbar vertebrae were increased in SHR treated with PRO at 0.1 and 1 mg/kg, suggesting antiosteoporotic action. PRO at 1 mg/kg statistically increased histomorphometry indices of bone formation, whereas PRO at doses of 0.1, 1, and 10 mg/kg decreased those of bone resorption. Antiosteoporotic effect of PRO is attenuated at 10 mg/kg compared with 0.1 and 1 mg/kg. In addition, treatment with timolol, a nonselective β-AR antagonist without membrane-stabilizing action, or butoxamine, a selective β2-AR antagonist, at 1 mg/kg increased bone mass in SHR. These results suggested that treatment of SHR with β-blockers at low dose improved bone loss and bone fragility. This antiosteoporotic effect of β-blockers seems to be caused by the blocking action of β2-AR, regardless of the membrane-stabilizing action. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics