Optimal distribution of blood flow requires coordination of vasodilation among resistance vessels. During hyperemia, blood vessels dilate upstream from the initiating stimulus. Spreading vasodilation independent of flow changes has not been previously demonstrated. In the present study, iontophoresis of acetylcholine adjacent to single hamster cheek pouch arterioles in situ (diameter, 20 to 37 micrometers) induced a rapid bidirectional dilation that was not attenuated when blood flow was eliminated with vascular occlusion. This finding indicates that a vasodilatory stimulus is conducted along the arteriole and demonstrates the existence of a mechanism of intercellular communication that is capable of coordinating diameter changes among resistance vessels.

Microvascular hematocrit and its possible relation to oxygen supply were systematically examined. We studied the red cell volume fraction (hematocrit) in arterial blood and in capillaries under a variety of circumstances. Control capillary hematocrit averaged 10.4 +/- 2.0% (SE) and arteriolar (14.2 micrometer ID) hematocrit averaged 13.9 +/- 1.2% in cremaster muscles of pentobarbital-anesthetized hamsters. Carotid artery hematocrit was 53.2 +/- 0.6%. The low microvessel hematocrit could not be entirely explained by a high red cell flux through arteriovenous channels other than capillaries (shunting). Hematocrit was not only low at rest, but varied with physiological stimuli. A 1-Hz muscle contraction increased capillary hematocrit to 18.5 +/- 2.4%, and maximal vasodilation induced a rise to 39.3 +/- 9.5%. The quantitative relations between capillary red cell flux, arterial hematocrit, and total blood flow could be explained by a two-element model of microvascular blood flow that incorporated a relatively slow-moving plasma layer (1.2 micrometer). Such a model would generate a low microvessel hematocrit and might reduce the diffusion capacity of individual capillaries, but would not reduce time-averaged red cell flux or alter steady-state vascular oxygen supply.

A method is described for the isolation and cannulation of microvessels (12-112 micrometers) that permits study, in vitro, of their physiology and pharmacology. Vessels from the hamster cheek pouch, testis, and mesentery and from rat brain have been isolated at 4 degrees C with specially prepared instruments and viewed with an inverted microscope. The vessels were cannulated at one end by equipment developed for renal tubular perfusion. The uncannulated end of the vessel is sealed, and experiments on reactivity and mechanics are carried out at fixed intravascular pressures. The isolated microvessels studied have a modulus of elasticity that is consistent with that observed in large vessels, and they display similar maximal active tension development (approximately 10(6) dyn/cm2). Reactivity to norepinephrine, acetylcholine, and adenosine are in the normal range for microvessels. Spontaneous tone is present, as evidenced by stable tonic contractions as well as phasic contractions in the frequency range of 3-30/min. The vessels display stress activation (myogenic response) consisting of contraction in response to increased intraluminal pressure. Our findings suggest that this preparation will be very useful in elucidating the physiology and pharmacology of the resistance vessels in the terminal vasculature.

A method is presented for the in vivo study of red cell flow dynamics. The method permits direct measurement of the red cell volume fraction in microvessel blood without resort to in vitro calibration curves. Furthermore, the method does not require extensive mathematical manipulation and can be applied to any microvascular network in any tissue. The method also enables direct measurement of red cell velocity, flux, and capillary transit time. Fluorescently labeled erythrocytes in tracer quantities, but known concentrations, are used as indicators of the behavior of the total cell population. Erythrocyte transit time across vascular networks and erythrocyte velocity are determined directly by following the behavior of the labeled cells. Hematocrit and red cell flux are measured by standard microcirculatory methods using labeled cells instead of the total cell population. Data are then converted to absolute values from the measured fraction of labeled cells. The method is thus absolutely dependent on the labeled cells being rheologically normal, and the conditions under which this requirement is satisfied are defined. Microvascular data obtained by the use of this method are presented for hamster cheek pouch and cremaster muscle.

Penetrating, intracerebral arterioles from rat were isolated, cannulated, and studied in vitro. Vessel wall elements were found to consist of an endothelial cell layer, one smooth muscle cell layer, and a thin adventitial layer or leptomeningeal sheath. Smooth muscle cell nuclei were oriented perpendicular to the vessel's longitudinal axis; endothelial cell nuclei were parallel to the axis. Mean vessel diameter with the smooth muscle inactivated (passive diameter) was 36.7 +/- 1.6 (SE) micrometer. Spontaneous smooth muscle tone developed at 37 degrees C and reduced vessel diameter to 70 +/- 4% of passive diameter. Vessels were activated by the extraluminal application of 140 mM KCl solution at pH 8.00, which produced a transient contraction that decayed within 30 s to a steady contraction of somewhat less intensity. Changes in intravascular pressure were used to alter wall tension of the vessels. Tension in the vessel wall was computed, and length-tension curves for the arteriolar smooth muscle were approximated. Length-tension relationships similar to those seen in other smooth-muscle preparations were found with maximal estimated force development of 1.29 x 10(-5) N . m-2. Alterations of bath pH caused changes in vessel diameter that were inversely related to extraluminal pH and varied by approximately 77% in the range from pH 6.85 to 8.00. Adenosine dilated vessels to 140 +/- 6% of control diameter at a concentration of 10(-5) M. The mechanical characteristics and the reactivity to H+, K+, and adenosine of these vessels were quantitatively consistent with in vitro data from larger cerebral vessels and in vivo data from pial arteries.