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The microvessels responsible for the major decrease in intestinal vascular resistance during the presence of glucose were defined. In addition, the normal distribution of tissue PO2 in the various layers of the intestinal tissue was measured at rest and during glucose exposure to determine if part of the absorptive hyperemia mechanism is related to a decrease in tissue PO2. In the rat small intestine, exposure of the mucosa only to glucose concentrations of 25--500 mg/100 causes a 20--25% dilation of all submucosal vessels in series with the mucosal vessels and mucosal arterioles. Total intestinal blood flow increased to 200-210% of control at all glucose concentrations. The tissue and perivascular PO2 in the villus apex decreased from 14.8 +/- 1.2 (SE) mmHg at rest to 6--8 mmHg during glucose exposure; the PO2 in the muscle and submucosal layers tended to slightly increase above a normal of 26.4 +/- 1.6 mmHg during glucose exposure. The data indicate virtually all intestinal arterioles are equally involved in absorptive hyperemia. The dilation of mucosal vessels may be related to a decrease in tissue PO2, but submucosal vessels dilate even though PO2 is slightly increased.

The results of direct pressure measurements are described which demonstrate that pressures in a certain fraction of mesenteric capillaries remain remarkably constant during large changes in systemic pressure. The results of isogravimetric studies, reported in the literature, are also described which indicate that this phenomenon may also occur in the intestine. The question is raised whether capillary pressures may therefore be regulated. Pressures recorded from mesenteric arterioles and capillaries are shown which indicate that maintenance of a constant capillary pressure is primarily the consequence of the vascular architecture peculiar to this tissue, and is merely a secondary reflection of mechanisms associated with flow regulation. The results of direct pressure measurements recorded in the microcirculation of intestinal muscle are also shown. These data indicate that capillary pressures in innervated, denervated, and xylocaine-treated intestinal muscle change in direct proportion to variations in arterial pressure. It is concluded that capillary pressures in the intestinal muscle layers are therefore not regulated, so that the observation that capillary pressures may be maintained is probably a phenomenon unique to the mesentery. Pressures recorded from capillaries in the mucosal villi are also shown and compared to capillary pressures measured in the microvasculature of mesentery and intestinal muscle. When systemic pressure was normal (107 +/- 10 mm Hg), capillary pressure in the mesentery averaged 30 to 33 mm Hg; capillary pressures in the intestinal muscle averaged 22 to 24 mm Hg; and capillary pressures in the mucosal villi averaged 13 to 15 mm Hg. These data suggest that mesenteric capillaries are primarily a filtering network; intestinal muscle capillaries are normally in fluid balance; whereas at rest mucosal capillaries are primarily absorptive. These pressures, recorded from the three major regions of the rat intestine, were used to calculate a weighted average for the whole organ. The calculated value, based on assumed values for relative capillary densities, was 17 mm Hg. This result compares favorably with data from whole organ, isogravimetric studies, and may clarify some of the apparent discrepancies between previous isogravimetric and servopressure studies.

This study was designed to determine if vessel wall hypertrophy and increased expression of sympathetic activity occur in the microcirculation during the development of hypertension. The cremaster muscle microvasculature of normal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was observed at age 5--7 weeks and 16--18 weeks. For age-matched WKY and SHR rats, the diameters, wall thicknesses and vessel wall cross-sectional areas for the majority of comparable types of arterioles were not significantly (p greater than 0.05) different. After denervation of the cremasteric muscle, the large and intermediate diameter arterioles of young WKY rats dilated significantly (p less than 0.05) more than did comparable vessels of SHR rats. In contrast, the dilation of comparable types of arterioles in mature WKY and SHR rats following denervation was not significantly (p greater than 0.05) different. The results do not support either abnormal vessel wall hypertrophy, vasoconstriction or increased expression of sympathetic activity in SHR rats compared to WKY rats up to age 16--18 weeks.

The responsiveness of the microvasculature and arteries during cerebral cortical autoregulation in rats was determined from measurements of microvascular pressures and blood flow as the systemic arterial pressure was altered. At systemic arterial pressures from 65 to 155 mmHg, cortical blood flow was essentially constant. Arterioles with a resting internal diameter of 20-70 microns responded by nearly equal proportional changes in diameter over this pressure range, but microvascular pressures were a linear function of arterial pressure. The percent of control changes in arterial and microvascular resistances at systemic pressures from 80 to 180 mmHg were nearly identical. Therefore, the microvasculature and arterial vasculature were approximately equally responsive to changes in arterial pressure over most of the autoregulatory pressure range. In addition, the arterial vasculature controlled 45-50% of the total vascular resistance at systemic arterial pressures from 40 to 180 mmHg. These data indicate that the cerebral vascular autoregulation in the rat depended substantially on the approximately equal responsiveness of the arterial vasculature and microvasculature. Similar results have been reported in cats and may indicate a common form of cerebral vascular control, which involves both the microvasculature and brain arteries among different species.

The present study details a new method for the exposure and viewing of individual microvessels located within the small intestine of rats. This procedure will selectively and consistently remove the outer muscle layers and underlying submucosa of the intestinal wall and thereby expose a variety of arterioles in their normal location within the tissue, with their normal relationship to each other undisturbed. The small intestine of the rat was initially fixed by vascular perfusion with 2.5% glutaraldehyde in 0.1 M cacodylate/HCL buffer, reinfused with heparinized whole blood, removed from the animal, and secured to a dissecting petri dish for further fixation. Subsequently, the external muscularis was dissected from the sample which exposed the submucosa. In order to remove the connective tissue elements from this layer and uncover the submucosal vasculature, the samples were first transferred to a solution of 30% potassium hydroxide for 2-5 minutes and then to a final digesting solution containing collagenase. Thereafter, the samples were routinely processed for light microscopy and for scanning (SEM) or transmission (TEM) electron microscopy. Examination of the samples revealed excellent preservation of the three-dimensional organization of the arteriolar wall with minimal membrane damage. This new technique now makes it possible to visualize the shape and position of individual smooth muscle cells along arterioles of differing size and branching order.

The potential presence of myogenic regulation in the cerebral microvasculature of the rat was investigated using a method which alters intravascular pressure without appreciably changing cerebral perfusion pressure (arterial minus venous pressure). The entire rat was placed in a sealed box, with the cranial cavity open to the atmosphere and prepared for in vivo microscopy. By increasing the ambient pressure in the box, both systemic arterial and venous pressure could be changed by nearly equal amounts (+/- 20 mm Hg). Heart and respiratory rates were not influenced by changing ambient pressure by +/- 20 mm Hg. At elevated ambient pressures, cortical arterioles constricted in linear proportion to the ambient pressure, whereas subatmospheric ambient pressures caused vasodilation whose magnitude was about equal at ambient pressures of -6 to -18 mm Hg. The calculated vessel wall tension typically remained within about +/- 10-15% of control during changes of transmural pressure of +/- 20-40%. In all cases, arteriolar responses to changes in ambient and intravascular pressure reached a new steady state within 10-15 seconds and were sustained for up to 30 minutes. These data are interpreted to indicate the presence of a myogenic vascular response in the brain vasculature of the rat.

The arterioles in the cremaster muscle of 8 to 10-week-old Ob/Ob, Db/Db and stroptozotocin diabetic mice are characterized by a decreased number of arterioles, loss of vascular tone and a reduced cross-sectional area of the vessel walls. The present study was designed to determine if these abnormalities persist to adult life or if additional abnormalities develop to cause vascular dysfunction. The diameters, wall thickness to lumen ratios and vessel wall areas of comparable types of innervated arterioles in 24- to 28-week-old normal and Db/Db mice are equivalent, except that the smallest arterioles of Db/Db have thin vessel walls. However, blood flow at rest is only 3.0 +/- 0.9 ml/min/100 g of cremasteric muscle tissue in Db/Db mice as compared to 5.5 +/- 1.3 ml/min/100 g in normal mice. After all vascular control is abolished, the arterioles of Db/Db dilated, but significantly (p less than 0.05) less than in normal animals. The minimum distance between adjacent capillaries (wall to wall) during the passive state was 28 +/- 1.7 micron in Db/Db mice and 21.8 +/- 0.6 micron in normal mice; this indicates a major decrease of vascularity in the adult Db/Db mouse. The results obtained indicate that the reduction in numbers of arterioles and loss of vascular tone in juvenile diabetic mice persists to adult life but arteriolar wall characteristics become normal in adult life.

Studies of the peripheral microcirculation in major organ systems during hypertension indicate that in anaesthetized spontaneously hypertensive rats (SHR) a combination of both vasoconstriction and temporary and permanent vessel closure occurs. The vasoconstriction is often limited to the largest and smallest arterioles and rarefaction is best expressed for arterioles with inner diameters less than 25 microns in the lower body musculature. Direct measurements of microvascular pressures in hypertensive rats indicate that while all arterioles in major organ systems are exposed to a pressure much higher than normal, the smallest arterioles dissipate a much higher than normal fraction of the mean arterial pressure. However, the transition vessels between the smallest arteries and the larger arterioles account for the largest fraction of total resistance (50-60%) and dominate the precapillary vascular resistance in the cerebral, intestinal and skeletal muscle vasculatures. In the established stages of hypertension, the relative influence of the transition resistance vessels is somewhat less than during the developmental phase of hypertension and also less than in adult normal animals. This latter observation has been made in a number of vasculatures and may indicate that resistance changes in the true microvessels and in the transition vessels do not occur simultaneously during the development of hypertension.

Microvascular pressures in the intestinal arteries, submucosal arterioles, and mucosal venules were measured in rats and rabbits at rest and during maximum dilation. From these data and Doppler velocimetry measurements of relative changes in whole organ blood flow on maximum dilation, it was possible to determine to what extent microvascular pressures at rest depend on the active control and passive hemodynamic characteristics of specific vascular segments. New Zealand White rabbits (2-3 kg body wt) had a mean arterial pressure of 70-75 mmHg. However, pressures in arterioles of both species became equivalent at the second order of arteriolar branching within the bowel wall, and pressures in the smallest mucosal venules were 13.7 +/- 0.6 (SE) mmHg in rabbits and 14.9 +/- 0.3 mmHg in rats. Maximum vasodilation to approximately 300% of the control blood flow increased mucosal venule pressures approximately 10 mmHg in rats compared with approximately 4 mmHg in rabbits. The increased mucosal venule pressure during vasodilation was primarily due to increased pressures within the submucosal small arterioles, which immediately precede the villus vasculature in both species. The increased blood flow during vasodilation was due primarily to a decreased resistance of the small arteries and large arterioles, even though pressures in these larger vessels changed only approximately 10%. This situation allows a major decrease in intestinal vascular resistance to substantially increase blood flow with a minimal increase in mucosal microvascular pressures.

Microvascular pathology is one of the major problems associated with prolonged diabetes mellitus. The purpose of the present study was to determine if anatomical cellular pathology of the cerebral cortical microvessels could be detected very early after the onset of a streptozotocin-induced model of diabetes. Male rats at age 14-16 weeks were hyperglycemic (greater than 250 mg/dl) for 4 weeks prior to scanning and transmission electron microscopic analysis of the external and internal cell and vessel wall morphology of the arterioles. Scanning electron microscopic studies indicated that many processes of vascular smooth muscle cells changed their normal spindle shape to a branched or stellate configuration. The internal cellular changes included swollen mitochondria and cisternae of the endoplasmic reticulum and reduced cytoplasmic staining. Necrosis of arteriolar endothelial cells was evident in virtually every vessel section studied. These data indicate that vascular smooth muscle and endothelial cellular degeneration of cerebral cortical arterioles begins in the very early stages of the streptozotocin model of diabetes.