Antagonist drugs and bone vascular smooth muscle.
An ex vivo canine tibia model was used to quantitate the specific adrenergic subtype contribution in bone vasculature. Tibiae were obtained from mongrel dogs, the nutrient artery was catheterized, and the bone was placed in an ex vivo perfusion apparatus at constant flow. Perfusion was accomplished using oxygenated Krebs-Ringer solution. A norepinephrine dose-response curve was obtained by using incremental single bolus doses. Each bone was perfused with a vasoactive drug at a standard physiologic dosage. After 30 min of perfusion, a second norepinephrine dose-response curve was generated. The degree of attenuation of the norepinephrine dose-response curve, as determined by the total area under the curve, was interpreted as the relaxation effect of the drug on the smooth muscle of the vascular bed. Prazosin (alpha 1-receptor antagonist), rauwolszin (alpha 2-receptor antagonist), propranolol (beta-receptor antagonist), and diltiazem (calcium-entry inhibitor) were evaluated. Our data suggest that alpha 1 and alpha 2 adrenergic receptor antagonism results in a quantitatively similar attenuation of norepinephrine-induced vascular smooth muscle contraction. Calcium-entry antagonism produced less, but significant, attenuation of smooth muscle contractility. Beta-adrenergic receptor blockade yielded only a slight, although consistent, reduction in reactivity. Simple perfusion with Krebs-Ringer solution had no effect.
Dean
M T
MT
Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905.
Wood
M B
MB
Vanhoutte
P M
PM
D000818:Animals; D001842:Bone and Bones / Q000098:blood supply*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008838:Microcomputers; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012984:Software; D013565:Sympatholytics / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D013565:Sympatholytics; D015016:Yohimbine; D004110:Diltiazem; D009638:Norepinephrine; D011224:Prazosin