Effects of propranolol on bone metabolism in spontaneously hypertensive rats.
The effects of propranolol (PRO), a nonselective beta-adrenergic receptor (beta-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 beta-AR antagonist without membrane-stabilizing action, or butoxamine, a selective beta2-AR antagonist, at 1 mg/kg increased bone mass in SHR. These results suggested that treatment of SHR with beta-blockers at low dose improved bone loss and bone fragility. This antiosteoporotic effect of beta-blockers seems to be caused by the blocking action of beta2-AR, regardless of the membrane-stabilizing action.
Sato
Takuma
T
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya, Japan.
Arai
Michitsugu
M
Goto
Shigemi
S
Togari
Akifumi
A
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol