The Journal of Bone and Joint Surgery, Vol 72, Issue 7 964-975, Copyright © 1990 by Journal of Bone and Joint Surgery, Inc
Pharmacological regulation of the circulation of bone
MR Brinker, HL Lippton, SD Cook and AL Hyman
Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112.
A study was undertaken to investigate the reactivity of the circulation of
bone and to pharmacologically characterize the receptor populations that
may be present in this poorly described vascular bed. The nutrient artery
of the tibia in skeletally mature mongrel dogs was cannulated, under direct
vision, through a posterolateral operative approach. An extracorporeal
circuit was established so that the nutrient artery of the tibia could be
perfused in vivo under conditions of constant blood flow. Diverse
vasoactive substances were injected into the perfusion circuit in small
volumes as a bolus close to the nutrient artery of the tibia. A range of
doses of nitroglycerin, acetylcholine, isoproterenol, methoxamine, U46619
(a thromboxane A2 mimic), dibutyryl cyclic AMP, 8-bromo-cyclic GMP, and
endothelin-1 were injected in a randomized sequence for each experiment.
The antagonists that were used were atropine (a non-selective muscarinic
receptor antagonist), ICI 118551 (a selective beta 2-adrenoceptor
antagonist), ONO 3708 (a prostaglandin H2/thromboxane A2 receptor
antagonist), and prazosin (an alpha 1-adrenoceptor antagonist). The results
of changes in bone-perfusion pressure under conditions of constant blood
flow indicated that the vascular bed of bone actively responds to various
vasoconstrictor mechanisms, whereas vasodilator mechanisms appear to be
considerably less active. Intra-arterial injections of nitroglycerin,
acetylcholine, and 8-bromo-cyclic GMP resulted in dose-related decreases in
bone-perfusion pressure that were weak relative to concomitant changes in
systemic arterial pressure. Intra-arterial administration of methoxamine,
U46619, and endothelin-1 resulted in a potent dose-related increase in
bone-perfusion pressure. The results of intra-arterial injections of
isoproterenol and dibutyryl cyclic AMP were surprising; both substances
caused a substantial rise in bone-perfusion pressure. The responses to
acetylcholine, methoxamine, and U46619 were blocked in a competitive manner
after administration of atropine, prazosin, and ONO 3708, respectively.
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