In: Blood Vessels And Lympatics In Organ Systems

By D. W. Lennox and D. S. Hungerford

This material has been published in Blood Vessels and Lymphatics in Organ Systems, edited by David I. Abramson and Philip B. Dorbin, the only definitive repository of the content that has been certified and accepted after peer review. Copyright and all rights therein are retained by Elsevier Science (USA). This material may not be copied or reposted without explicit permission.

Copyright 1984, Elsevier Science (USA). All rights reserved.

It has been known for many years that neurohumoral and metabolic factors regulate blood flow to bone (Drinker and Drinker, 1916), but only with the advent of sophisticated blood flow measurement techniques have the specific effects upon bone blood flow of a number of hormones and other neuropharmacologic agents been investigated.


Gross et al. (1979, 1981) demonstrated that, in the dog, norepinephrine infusion increases vascular resistance to bone and marrow by two times the baseline value, whereas the potent vasodilator, adenosine, on infusion, diminishes vascular resistance by one-third. Similarly, Driessens and Vanhoutte (1977, 1979) noted in dog tibias increased perfusion pressures in response to norepinephrine, a response that was blocked by phentolamine and inhibited by acetylcholine. In addition, the acetylcholine effect was abolished by atropine. Intraarterial acetylcholine was found to induce bone blood vessel dilatation by Michelsen (1968). Calcitonin produced dose-dependent elevations in perfusion pressure in dog tibias (Driessens and Vanhoutte, 1981) and a decrease in skeletal blood flow in patients with Paget’s disease (Wootton et al., 1976a, 1978). Bone blood vessel dilatation in response to parathvroid hormone was reported by Boelkins et al. (1976).

The effect of hydrocortisone on bone blood vessels was studied by Driessens and Vanhoutte (1981). They found that at low concentrations, the drug augmented the vasoconstrictor response to norepinephrine, whereas, at high concentrations, it had the opposite effect.

Dusting et al. (1978) investigated the action of arachidonic acid and several related metabolites on the femoral vasculature in the dog. They noted vasodilatation with injections of PGI2 PGE2, sodium arachidonate, and the endoperoxide PGH2. Utilizing the femoral vascular bed of the dog as a model, Laubie et al. (1977) studied the effect of apomorphine and piribedil (ET 495) as dopamine agonists and, on the basis of their results, proposed the existence of depamine receptors involved in mediating vasodilator and sympathoinhibitory effects.


Tonic sympathetic vasoconstriction of blood vessels of bone in anesthetized dogs was demonstrated by Gross et al. (1979). On stimulation of carotid baroreceptors, a one-third reduction in vascular resistance in bone was noted, as compared with a corresponding 80% decrease in skeletal muscle vascular resistance under similar conditions. In cats, deafferentation of baroreceptors to activate sympathetic nerve discharge produced heightened vascular resistance. Increased perfusion pressure in the nutrient artery of the dog tibia following periarterial electrical stimulation was noted by

Driessens and Vanhoutte (1979). This response was blocked by phentolamine and hence was presumed to be due to sympathetic activation. An augmentation in tibial blood flow following lumbar sympathectomy was reported by Trotman and Kelly (1963). In accord with such a finding is the earlier observation of vasoconstriction in bone blood vessels after sympathetic stimulation (Drinker and Drinker, 1916; Weiss and Root, 1959).


Evidence exists for the control of bone blood flow by a number of metabolic factors, including acidosis and hypercapnea. Cumming (1962), studying the effect of rebreathing expired air, or breathing a low oxygen-high carbon dioxide gas mixture on the femoral nutrient vein outflow in the rabbit, reported a 20% increase in outflow under such conditions. This finding was confirmed by Shim and Patterson (1967), who noted increased blood flow in rabbit bone following rebreathing of expired air. Gross et al. (1979) studied the changes in bone and marrow blood flow and resistance in the baboon in response to arterial acidosis and hypercapnea induced by adding 10% CO2, to inspired air while maintaining constant and normal arterial oxygen concentration. At arterial pCO2 = 65 1 mm Hg and pH 7. 14 0.02, they noted a statistically significant increase in bone blood flow to sternum, rib, and femoral marrow and a marked decrease in calculated vascular resistance. Variations in bone blood flow in response to a number of factors are presented in Table 20.1


TABLE 20.1
Variations In Bone Blood Flow In Respone To A Number of Factors

Sympathetic stimulation


Regulatory mechanisms for the control of blood flow to bone and marrow thus appear to be highly integrated and responsive, involving nervous, humoral, and metabolic factors. The development of new techniques of blood flow assessment has resuIted in the discovery of additional pharmacologic data on bone blood flow.

Future advances will doubtless include study of the complex interplay among humoral, neural, and metabolic factors in regulating bone blood flow. As new pharmacologically active agents are discovered or previously known ones reassessed, pharmacologic intervention in altered bone blood flow states may become possible, as for example, in the case of bone neoplasms, osteoporosis, fractures, growth, and aging.


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