Erythrocyte-containing capillaries were counted in dog gracilis muscles freeze-clamped at rest and after twitch contraction at 4/s. In each of 21 muscles, 6--8 blocks were examined at -70 degrees C without fixation or staining; 15 fields were counted per block. Frequency analysis of capillaries per field based on the negative binomial distribution indicated that capillary density at rest was controlled by arterioles. Active vasomotion of these arterioles was "switched off" within 5 s after onset of exercise. Capillary density was then determined passively by stochastic rheologic factors acting at the individual capillaries. Thus exercise changes the site and the mechanism of capillary control. Recruitment occurred first where capillary density was lowest, and was complete in 15 s; this greatly decreased the heterogeneity of capillary spacing. Mean capillary density increased 1.5- to 3-fold, whereas flow increased almost 7-fold. Calculated mean velocity and mean transit time of erythrocytes in capillaries were 1.1 mm/s and 920 ms at rest and 4.2 mm/s and 215 ms after 3 min of exercise.

Capillary control was quantified in dog gracilis muscles from in situ. About 550 capillaries/mm2, one-third the total number present, were perfused with erythrocytes simultaneously at rest; two-thirds the total could be perfused during maximal vasodilation. The functional capillary reserve was about 600/mm2. Capillary distribution at rest reflects a passive, random process at individual capillaries and an active process that coordinates perfusion of small groups of capillaries. The latter creates long diffusion distances. These are unaltered by denervation, or flow per se, but are abolished by adenosine. Twitch contraction at 4/min recruited about 400 capillaries/mm2 without any change in flow. Capillaries opened selectively where diffusion distances were longest. The same changes occurred within 5 s during work at 4/s, even if flow was held constant. If flow could increase, about 200 additional capillaries/mm2 were slowly recruited, without change in capillary distribution. Conclusions are that 1) hemodynamics and active vasomotion contribute equally to capillary density at rest; 2) active papillary control in exercise is ungraded and solely responsible for eliminating metabolically significant diffusion paths; 3) flow and capillary density can be controlled independently by proximal and terminal arterioles, respectively.

Theophylline, quinidine, and dipyridamole were used to evaluate the role of adenosine in exercise vasodilation in dog gracilis muscles perfused at low, constant flow. Theophylline, 10(-3) M in blood, blocked adenosine vasodilation completely, but did not alter the magnitude or rate of vasodilation aroused by brief tetani, or by 1 min of twitch contraction. Quinidine's effects were too nonspecific to interpret in terms of the adenosine hypothesis. Dipyridamole increased and prolonged vasodilation due to injected adenosine, but did not increase the magnitude of exercise vasodilation known to be submaximal. In about half the muscles tested, dipyridamole slowed recovery of resistance after contraction stopped. Bioassay data strongly suggest it did so by enhancing the contribution of a purine metabolite. Results are interpreted to mean that adenosine does not influence the rate or magnitude of exercise vasodilation, but may prolong recovery from heavy work at constant flow. The generality of results and interpretations is discussed.

Total capillary length, capillary segment length, and number of anastomoses per capillary were measured in rat gracilis muscle at rest and after 2 min of phasic contraction. Mean values of the foregoing variables at rest (+/-SD) were, respectively, 1,012 micronm +/- 484, 409 micron +/- 274, and 0.83 +/- 1.09. Total capillary lengths are well described by the gamma distribution, number of anastomoses by the negative binomial distribution, and segment length by the Weibull distribution. Contraction has no significant effect on the means or the frequency distributions, indicating that: 1) pressure gradients between adjacent capillaries are small, and 2) intercapillary anastomoses do not improve flow distribution in exercise. Erythrocyte velocities observed in resting muscle (Burton, K. S., and P. C. Johnson. Am J. Physiol. 223: 517-524, 1972) were shown to be adequately characterized by the gamma distribution. From these velocities and the observed distribution of path lengths, we computed an estimated distribution of capillary transit times. Mean transit time was 4.29 s. The median was 2.45 s, and 11% of values exceeded 8 s. The range was 90 ms-43 s. This heterogeneity of transit times should profoundly affect calculations of O2 transport and the shape of indicator dilution curves.

Ganglion cells exist in muscle arterioles. To determine the role of these intrinsic neurons in postcontraction vasodilation, isolated dog gracilis muscles were studied. A single twitch elicited vasodilation, but no vasodilator metabolites appeared in the venous effluent. Contraction at 2/s lowered resistance within 1 s whereas dilator metabolites were not demonstrable in the effluent until 15-20 s. During contraction the magnitude and time course of vasodilation were the same during constant and variable flow, and at various values of PaO2 and PVO2. In contrast, resistance was strongly correlated with flow and PO2 during recovery. Some resting muscles were perfused with venous blood from contracting donors. The rate of metabolic vasodilation in recipient muscles was about 10 times less than the rate of vasodilation in the donors. Lidocaine and procaine blocked postcontraction vasodilation but did not influence postocclusion vasodilation, metabolic vasodialtion, or autoregulation. The degree of block was the same in acutely and chronically denervated muscles. The effect of local anesthetics could not be accounted for by properties of skeletal or vascular smooth muscles. Conclusions: 1) intrinsic neurons initiate postcontraction vasodilation; 2) metabolites account for sustained vasodilation during recovery.