3.1. BASAL HEMODYNAMICS AND OXYGENATION
Estimates of blood flow (in ml /min × 100 g) to the quiescent gastrointestinal tract of dogs and cats range from 15 to 100 for the stomach, 35–120 for the small intestine, and 10–74 for the colon [7,22–24]. Somewhat lower values for resting blood flow to the stomach (11), small intestine (29–70), and colon (8–35) have been reported for man . Although reported resting values vary between and within a given species, it is generally agreed that small intestinal blood flow exceeds that of the stomach or colon. Further, as mentioned above, throughout the gastrointestinal tract, the mucosal layer receives a greater portion of the total wall flow than the muscularis region.
The delivery of oxygen and nutrients to the gastrointestinal parenchyma is determined not only by blood flow but also by the number of capillaries opened to blood perfusion (capillary density). It is generally assumed that approximately 25–50% of the capillaries in the quiescent gastrointestinal tract are open to perfusion . Experimentally, the capillary filtration coefficient (Kf,c) can provide an index of capillary density or functional exchange capacity in a tissue [26,27]. Kf,c has been assessed in the stomach, small intestine, and colon using volumetric or gravimetric techniques. These approaches involve a rapid increase in venous pressure, while measuring changes in organ volume or weight. The slope of the volume (or weight) increase (attributed to capillary filtration) is divided by the increment in capillary pressure to yield Kf,c. One caveat to this approach is that Kf,c is a measure of transcapillary hydraulic conductance and, as such, is influenced by both the capillary surface area available for exchange as well as the capillary permeability to solutes and fluid [26,27]. In general, however, unless the experimental maneuvers involve changes in permeability (e.g., injury, inflammation, agents that affect endothelial integrity), changes in Kf,c are taken as changes in perfused capillary density or exchange capacity.
The resting values of Kf,c range from 0.03 to 0.30 ml/min /100 g for the small intestine of cats, dogs, and rats [28–30]. A similar range of Kf,c values have been reported for the dog stomach and colon [31–34]. The relative uniformity of the ranges of the mean values for Kf,c among the different regions of the gastrointestinal tract preclude any definitive statements regarding their relative capillary surface areas.
Oxygen consumption or demand of gastrointestinal organs can be calculated as the product of blood flow (QB) and the arteriovenous oxygen difference ((A – V )O2). Resting values of oxygen consumption of the stomach, small intestine, and colon in the dog and cat are fairly uniform; ranging from 1.5 to 2.5 ml/min × 100 g [35–40]. There are no apparent differences in the resting values for oxygen consumption among the various regions of the gastrointestinal tract. Oxygen consumption of the rat small intestine is about 4.8 ml /min × 100 g , values two to three times higher than those reported for larger animals.
3.2. INTRINSIC VASOREGULATION: MYOGENIC AND METABOLIC
Gastrointestinal blood flow and oxygenation are maintained within relatively narrow limits by vasoregulatory mechanisms operating at the organ/tissue level. Existence of intrinsic regulatory systems has been established by experiments in isolated organs or blood vessels. Data obtained from experimental studies have been incorporated into mathematical models allowing for predictions of microcirculatory behavior not amenable to experimentation. Based on both experimental and computer modeling approaches, two major mechanisms have been invoked to explain the ability of the gastrointestinal tract to regulate its vasculature to meet tissue demands: the myogenic and metabolic (Figure 3.1) [7,25,41–49].
Isolated mesenteric arterioles respond to elevations in transmural pressure with vasoconstriction and vice versa; the response being the most intense in the smaller resistance vessel . This phenomena is referred to as the myogenic response [51–53]. The myogenic response is an intrinsic property of vascular smooth muscle, since it occurs in mesenteric arterioles that have had their endothelial lining removed . The myogenic response is based on the law of LaPlace, which contends that tension development in smooth muscle is the product of the intravascular pressure and vessel radius (Figure 3.1). Thus, increases in intravascular pressure lead to decreases in radius (constriction) in an attempt to maintain tension. Conversely, decreases in vascular transmural pressure result in dilation to maintain tension.
If a myogenic mechanism is operative in the microcirculation of the gastrointestinal tract, an increase in microvascular transmural pressure would result in increases in vascular resistance and vice versa (Figure 3.1). Since as much as 70% of the increase in venous pressure can be transmitted back upstream to the capillaries and resistance vessels, a commonly used experimental maneuver is to increase venous pressure in isolated preparations of the stomach, small intestine, or colon. To determine whether resistance vessels are affected by acute venous hypertension, arterial and venous pressures (arteriovenous pressure gradient; ΔP) as well as blood flow (QB) are measured and resistance calculated (R = ΔP/QB). To assess the myogenic impact on exchange vessels, the capillary filtration coefficient (Kf,c) can be measured. The existence of a myogenic regulatory system has been experimentally verified in the stomach , small intestine [27,54,55], and colon [40,56,57].
Almost invariably, there is an increase in vascular resistance (and decrease in blood flow) when venous pressure is elevated (Figure 3.2). In addition to the regulation of resistance vessels, the myogenic response may play a role in regulating precapillary sphincter tone and thereby capillary exchange capacity. There is evidence to support an increase in precapillary resistance (decrease in Kf,c) during acute venous hypertension . However, elevations in microvascular transmural pressure increase, rather than decrease, capillary exchange capacity in the stomach and the colon (Figure 3.2) [41,42]. The latter responses are rather inconsistent with the generally held view that smaller blood vessels are more sensitive to the alterations in transmural pressure then larger vessels, i.e., the smaller vessels exhibit greater myogenicity [52,53].
The physiologically significant roles attributed to intrinsic myogenicity of blood vessels in the gastrointestinal tract are (1) establishment and maintenance of basal vascular tone and (2) regulation of blood flow during acute changes in perfusion pressure [52,58]. An extension of the latter role of the myogenic response may be to dampen the arterial pulse pressure at the level of the microcirculation thereby ensuring a more uniform flow distribution to the capillaries . It is noteworthy that while the myogenic mechanism plays an important role in maintaining capillary pressure (and glomerular filtration rate) in the kidney , autoregulation of capillary pressure (and capillary filtration rate) in the small intestine is rather poor .
The metabolic theory of local blood flow holds that tissue oxygenation, specifically tissue pO2, is the regulated variable (Figure 3.1). According to the metabolic theory, an increase in metabolic activity (increased O2 demand) would lead to an increased (1) consumption of O2 by the mitochondria resulting in a decrease in tissue pO2 and (2) generation of vasodilator by-products of metabolism. The subsequent increases in blood flow (resistance vessels) and capillary surface area (precapillary sphincters) would tend to increase tissue pO2 and washout out vasodilator metabolites, thereby closing the feedback loop [25,42,43,61,62].
Both arteriolar resistance and precapillary sphincters play a role in the regulation of tissue oxygenation. Resistance vessels regulate the convective delivery of arterial O2 to capillaries by modulating blood flow. Thus, the rate of oxygen delivery to capillaries is the product of blood flow and arterial O2 concentration. Precapillary sphincters regulate the diffusive delivery of oxygen to cells/tissues by modulating the number of perfused capillaries. The number of perfused capillaries determines the effective capillary surface area available for oxygen diffusion as well as the diffusional distance for O2 from capillaries to cells. If a metabolic mechanism is operative in the microcirculation of the gastrointestinal tract, an increase in the tissue O2 demand-to-delivery ratio would result in decreases in vascular resistance and recruitment of capillaries (Figure 3.1).
The relative roles of resistance vessels and precapillary sphincters in maintaining tissue oxygenation during alterations in O2 demand or O2 delivery have been assessed by measurements of relevant parameters in isolated perfused preparations of the stomach, small intestine, or colon. Changes in resistance vessel tone can be assessed by measuring perfusion pressure and organ blood flow (QB). The capillary filtration coefficient (Kf,c) provides an estimate of capillary surface area. Despite the potential influence of vascular permeability on Kf,c, changes in Kf,c under normal conditions (e.g., noninflammatory) is generally attributed to alterations in the number of perfused capillaries. In support of this contention is the observation that there is a direct linear correlation between Kf,c and oxygen extraction [36,63]. O2 consumption (or demand) can be calculated as the product of QB and the arteriovenous O2 difference [(A − V )O2]. The O2 delivery-to-demand ratio can be readily calculated as the quotient of O2 demand and O2 delivery. The existence of a metabolic regulatory system has been experimentally verified in the stomach [35,64,65], small intestine [36,44,60,63,66], and colon [40,56,67]. A synopsis of these studies is presented below using the small intestine as a prototype of the gastrointestinal tract.
A common experimental maneuver to alter the O2 delivery-to-demand ratio is to alter gastrointestinal blood flow (or O2 delivery) either mechanically (pump-perfused preparations) or by graded stenosis of the arterial supply (naturally perfused preparations). In naturally perfused preparations, moderate decreases in perfusion pressure are associated with dilation of resistance vessels in an attempt to maintain O2 delivery, and the capillary exchange capacity increases to enhance O2 diffusion to cells. With substantial decreases in perfusion pressure, the decrease in vascular resistance is insufficient to maintain a constant organ blood flow, i.e., blood flow tends to decrease. Despite the fall in blood flow, oxygen consumption tends to remain at control levels due to increases in capillary exchange capacity (Kf,c) and an increase O2 extraction by the tissue (Figure 3.3). Similar results have been noted in pump-perfused preparations with the added benefit of demonstrating that increases in blood flow (or O2 delivery) are associated with decreases in O2 extraction such that O2 uptake is unaffected (Figure 3.3).
Metabolic regulatory mechanisms become exhausted with severe reductions in blood flow (O2 delivery), and as a consequence, O2 consumption (or O2 demand) begins to decrease (Figure 3.3). At this point, oxygen consumption is directly dependent on blood flow (O2 delivery). The resting blood flow of the gastrointestinal tract is greater than the critical level at which oxygen uptake becomes blood flow dependent. The reduction in oxygen uptake below a critical blood flow has been attributed to the effects of cellular pO2 on mitochondrial O2 consumption. The relationship between cell pO2 and mitochondrial O2 consumption is independent of cell pO2 until a critically low cell pO2 is achieved at which point mitochondrial O2 uptake (consumption) is compromised. It is generally believed that resting cell pO2 in the gastrointestinal tract is above the critical cell pO2 . For example, modest reductions in blood flow to the stomach reduce gastric epithelial cell pO2 without compromising whole organ oxygen consumption . However, when metabolic control of the microvasculature is inadequate to maintain capillary and tissue pO2 above a critical level, diffusion of O2 to cells is no longer adequate to maintain normal mitochondrial O2 metabolism.
Another approach to alter the O2 delivery-to-demand ratio is to simultaneously alter gastrointestinal O2 demand and delivery (Figure 3.4) [63,69]. Increases in O2 demand (enhanced secretory, absorptive, or motor activity) simply shift the plateau of the delivery (blood flow) to demand relationship upward [35,38,63], while decreases in the O2 demand (temperature reduction) shift the plateau downward . Collectively, these responses are consistent with the metabolic theory, i.e., tissue oxygenation, rather than blood flow per se, is the regulated variable.
Although in the experimental situation one can readily alter blood flow or the oxygen carrying capacity of the blood, it is virtually impossible to control capillary density. Indirect approaches are used to assess the role of exchange vessels in meeting the oxygen demands of the gut. For example, in constant flow preparations, increases in O2 demand (nutrient absorption) or decreases in O2 delivery (hypoxia) are associated with increases in capillary density as estimated by Kf,c or 86Rb extraction [70,71]. Based on mathematical modeling approaches , the expected influence of capillary density on the relationship between O2 demand and O2 delivery is depicted in Figure 3.4. If capillary density is increased then a greater reduction in blood flow or O2 delivery would be tolerated before O2 consumption was compromised; i.e., the curve would be shifted to the left.
The most significant physiological role attributed to metabolic regulation of blood vessels is the maintenance of an optimal tissue oxygenation during alterations in the O2 demand-to-delivery ratio.
3.3. RELATIVE IMPACT OF MYOGENIC AND METABOLIC MECHANISMS
A variety of experimental perturbations have been used to assess the relative roles of the metabolic and myogenic mechanisms in the regulation of the gastrointestinal microcirculation. These include reactive hyperemia, vascular responses to venous pressure elevations, and pressure-flow autoregulation. It is becoming increasingly apparent that the myogenic and metabolic mechanisms may operate synergistically or in opposition to elicit a particular vascular response.
3.3.1. Reactive Hyperemia
The term “reactive hyperemia” refers to the transient increase in flow above basal levels after the release of an arterial occlusion. All of the regions of the gastrointestinal tract exhibit a reactive hyperemia after brief periods of arterial occlusion; the magnitude and duration of the hyperemia are directly related to the duration of the occlusion . Both myogenic and metabolic hypotheses predict vasodilation upon release of an arterial occlusion; the myogenic based on the occlusion-induced fall in arteriolar transmural pressure and the metabolic based on the fall in tissue pO2 and /or increase in vasodilator metabolites. However, only the metabolic mechanism can account for the direct relationship between the duration of occlusion and the magnitude of the hyperemia.
The reactive hyperemic response in the small intestine appears to be limited to the mucosal layer of the bowel wall . The magnitude of the reactive hyperemia in the mucosa was related to the duration of arterial occlusion. This indicates that the microvasculature of the more metabolically active mucosa is more sensitive to metabolic factors. Further support for this contention is the observation that increasing the metabolic rate of the small intestine (mucosal nutrient transport) increases the magnitude of the reactive hyperemic response; which was again confined to the mucosal layer of the gut .
3.3.2. Venous Pressure Elevation
The myogenic and metabolic hypotheses predict opposite microvascular adjustments to increases in venous pressure. The myogenic hypothesis predicts that arteriolar resistance should increase, and capillary density should decrease in response to elevations in venous pressure due to the rise in intravascular pressure at the arteriolar and precapillary sphincter levels. By contrast, the metabolic hypothesis predicts that the elevation of venous pressure should decrease arteriolar resistance and increase capillary density due to the reduced blood flow and accumulation of vasodilator metabolites and /or decrease in tissue pO2. In the stomach, small intestine, and colon, acute venous hypertension results in an increase in arteriolar resistance and decrease in organ blood flow (Figure 3.2), findings consistent with a myogenic mechanism. Isolated segments of mesenteric arteries also exhibit a myogenic vasoconstriction in response to increases in transmural pressure . The response of the more sensitive microvascular elements (precapillary sphincters) to acute venous hypertension varies with the segment of the gastrointestinal examined. An increase in venous pressure results in a decrease in capillary exchange capacity in the small intestine, again, consistent with a myogenic mechanism. However, oxygen uptake by the small intestine is not compromised [44,61]. By contrast, acute venous hypertension in the stomach and colon results in an increase in capillary density (Figure 3.2). These latter findings indicate that the precapillary sphincters in the colon and stomach are more sensitive to metabolic factors, than those of the small intestine. Collectively, the experimental data indicate that both the myogenic and metabolic mechanisms are acting in concert in the quiescent gastrointestinal tract.
The microvascular response to acute venous hypertension is affected by the preexisting metabolic demand. When the O2 demand of the small intestine and colon is increased, the characteristic increase in vascular resistance to acute venous hypertension is abolished [44,56]. For example, as shown in Figure 3.5, local administration of dinitrophenol or placement of digested food in the lumen prevents the increase in vascular resistance noted after acute venous hypertension. These findings indicate that when the small and large intestine are metabolically stressed, metabolic control overrides myogenic control of the local microcirculation.
3.3.3. Arterial Pressure Reduction
The ability of an organ to maintain a relatively constant blood flow in the face of fluctuations in arterial pressure is termed “pressure-flow autoregulation.” Pressure-flow autoregulation has been demonstrated in the stomach , small intestine [29,60,74–76], and colon [40,56,57,77]. Both the myogenic and metabolic theories predict a similar vascular response during reductions in arterial pressure. According to both theories, a decrease in perfusion pressure should decrease arteriolar and precapillary sphincter resistance. The myogenic response would be elicited due to decreases in transmural pressure invoked by the local hypotension. The metabolic response would be elicited due to the initial local decrease in blood flow (O2 delivery) resulting in a decrease in tissue pO2 and /or build up of vasodilator metabolites. However, based on the following lines of evidence, it is generally believed that the metabolic mechanism prevails over the myogenic to elicit autoregulation. First, the autoregulatory ability of the more active mucosal layer of the stomach , small intestine , and colon  exceeds that of the whole organ. Second, when the metabolic demand of the small intestine [76,80] or colon  is increased by feeding or luminal instillation of transportable solutes, their autoregulatory ability is enhanced. Third, while autoregulation of blood flow is generally not perfect at lower perfusion pressures, oxygen uptake remains within normal limits [36,40,81]. The maintenance of tissue oxygen uptake despite the fall in blood flow is due to increases in capillary density [36,40,63].
In summary, both the myogenic and metabolic mechanisms play a role in intrinsic regulation of the gastrointestinal circulation. The myogenic mechanism appears to play a role in basal vascular tone and the regulation of transmural pressure in resistance vessels. The metabolic mechanism serves to maintain tissue oxygenation by regulating oxygen delivery to meet changes in oxygen demand. Unlike the case in the renal vasculature where myogenic regulation of capillary transmural pressure is critical , the myogenic mechanism appears to be readily overridden by metabolic factors in the gastrointestinal tract.
3.4. MEDIATORS OF METABOLIC VASOREGULATION
Of the various vasoactive mediators that have been proposed to be involved in mediating intrinsic metabolic regulation of the gastrointestinal microcirculation, tissue pO2 and vasodilator metabolites (specifically, adenosine) have received the most attention [42,61,62]. In addition, nitric oxide (NO) has been implicated as a major mediator of metabolic vasoregulation. In general, neither tissue pO2, adenosine, nor NO meets all of the criteria for being the decisive mediator of metabolic vasoregulation. More than likely, all three of them may act in concert or opposition depending on the prevailing situation. Evidence in favor of and against their participation in metabolic regulation of the gastrointestinal tract microcirculation is presented below.
3.4.1. Tissue pO2
Mathematical models predict that tissue pO2 may be a direct link between metabolic activity of the gastrointestinal tract and microvascular tone [25,82]. Direct measurements of tissue pO2 (microelectrodes) indicate that there is an inverse correlation between villus pO2 and the rate of blood flow through submucosal vessels supplying the villus [83,84]. Further, small intestinal oxygen demand (glucose absorption) reduces villus pO2 and increases blood flow through submucosal vessels supplying the villus. However, blood flow to the muscularis layer of the small intestine also increases despite an unaltered tissue pO2 in the vicinity. Further, maintenance of mesenteric pO2 by alteration of ambient oxygen did not effect pressure-flow autoregulation in mesenteric blood vessels . Although the mesentery is primarily connective tissue (little metabolic activity), collectively, these latter observations do suggest that other factors, besides tissue pO2, may be involved in intestinal vasoregulation.
Metabolic by-products may also provide an indirect link between metabolic activity of the gastrointestinal tract and microvascular tone. With respect to potential vasoactive metabolites, adenosine, a potent intestinal vasodilator , has received the most attention. Intestinal interstitial adenosine levels are increased during reactive hyperemia  and increased metabolic demand of nutrient transport  as reflected by increased venous and lymphatic adenosine concentrations. Adenosine blockade decreases the reactive hyperemic response  and either decreases or has no effect on the hyperemia associated with luminal nutrients [89,90]. Similarly, adenosine blockade either decreases  or does not affect  intestinal pressure-flow autoregulation. This ambiguity has an apparent resolution in the observations that adenosine blockade consistently diminishes the reactive hyperemic response and pressure-flow autoregulation in the hypermetabolic (nutrient absorption) small intestine [89,92]. It has been proposed that while adenosine does not play a role in vasoregulation under resting conditions or during moderate changes in the O2 delivery-to-demand ratio, it has a significant contribution to the vasodilation induced by more severe stresses .
One disconcerting aspect regarding the potential role of adenosine in intestinal vasoregulation is that upon intra-arterial infusion, it appears to (1) redistribute blood flow from the mucosa to the muscularis and (2) decrease capillary exchange capacity and tissue oxygen consumption [93,94]. It has been proposed that adenosine is a more potent vasodilator of the muscular layer than the mucosal layer, and during intra-arterial infusion, adenosine induces a “vascular steal” response redirecting blood flow to the muscularis which is less (1) metabolically active and (2) vascularized. The situation may be quite different during local compartmentalized release of adenosine during nutrient transport by the mucosa or contractions of the muscularis. For example, during nutrient transport, mucosal adenosine levels would be increased locally and produce a hyperemia confined to the mucosal layer; blood flow to the muscularis should remain unaltered.
3.4.3. Nitric Oxide
Another potential mediator of intrinsic vasoregulation in the gastrointestinal tract is NO released from endothelial cells [61,62]. NO is synthesized from L-arginine by endothelial nitric oxide synthase (eNOS) [95,96]. The NO generated by the endothelial cells diffuses to the vascular smooth muscle, where it induces vascular smooth muscle contraction via cGMP-dependent protein kinase signaling pathway resulting in decreases in intracellular Ca++ concentration.
Based on the use of inhibitors of eNOS (e.g., L-NAME), endothelial-derived NO appears to play a role in basal vascular tone in the stomach  and small intestine . A major stimulus for NO release by endothelial cell eNOS is vessel wall shear stress (or blood flow);  the resultant flow-mediated vasodilation is more prevalent in resistance arterioles than precapillary sphincters [99,100]. Thus, it would be predicted that decreases in blood flow (and O2 delivery) would inhibit shear stress-mediated NO production and result in vasoconstriction. By contrast, hypoxia can result in endothelial NO production independent of shear stress and result in an NO-mediated dilation of isolated blood vessels . In vivo, inhibition of NOS (e.g., L-NAME) potentiates pressure-flow autoregulation, indicating that NO is not mediating pressure-flow autoregulation, but actually opposing it . Thus, during decreases in O2 delivery, NO does not seem to play a role in the metabolically mediated vasodilation.
However, there is some convincing evidence that NO may play a role in the hyperemia associated with increases in O2 demand. The hyperemia associated with small intestinal absorption of glucose [103–105] or gastric acid secretion [97,106] is associated with local generation of NO and can be attenuated by blockade of NO bioactivity.
3.5. MEDIATORS OF MYOGENIC VASOREGULATION
As mentioned above, the myogenic response is an intrinsic property of vascular smooth muscle, since it occurs in mesenteric arterioles that have had their endothelial lining removed . In this context, vascular smooth muscle is generally believed to be both the sensing (tension sensor) and effector (contractile response) element. The signaling mechanisms, which transduce changes in transmural pressure into smooth muscle contraction, are largely unknown. A model of mechanosensing has been proposed, which includes roles for extracellular matrix /integrins, smooth muscle cytoskeleton, and mechanosensitive enzyme systems, transporters, and channels. The current status of this area has been recently reviewed .
However, the myogenic response in intact blood vessels in vivo may be more complex. For example, endothelial-derived NO may modulate the myogenic-induced vasoconstriction. An increase in stretch of blood vessels results in endothelial production of NO in situ  as does increased endothelial cell deformation or cyclic strain in vitro [108,109]. In this case, NO would be serving to antagonize the smooth muscle myogenic vasoconstriction.
3.6. SHEAR STRESS MODULATION OF METABOLIC AND MYOGENIC REGULATORY SYSTEMS
It is becoming apparent that endothelial wall shear stress imposed by the flowing blood can modulate microvascular tone. For example, an increase in shear stress results in a dilation of resistance vessels, which results in returning wall shear stress toward original levels . It is generally believed that this vasoregulatory phenomenon is mediated via the release of vasodilator substances from the endothelium, such as prostaglandins and NO . Endothelial-derived NO appears to be more important than prostaglandins in flow-induced vasodilation in isolated mesenteric arteries .
The precise mechanisms by which endothelial cells transduce shear stress into adjacent smooth muscle contraction are not entirely clear, but the endothelial glycocalyx, extracellular matrix components, integrins, and cell junctional molecules may be involved . For example, NO production and flow-dependent vasodilation of mesenteric arteries is inhibited by enzymatic degradation of the endothelial glycocalyx [113,114]. Evidence is also accumulating to indicate that platelet-endothelial cell adhesion molecule-1 (PECAM-1), an endothelial cell junctional molecule, may be a key endothelial cell mechanoresponsive molecule. First, mechanical “tugging” of endothelial cell PECAM-1 with magnetic beads results in activation (phosphorylation) of PECAM-1 . Second, shear stressed-induced phosphorylation of PECAM-1 enhanced PECAM-1 association with and phosphorylation of eNOS as well as NO production, events not noted in PECAM-1-deficient endothelial cells . Finally, flow-induced vasodilation is significantly blunted in isolated arterioles from PECAM-1-deficient mice .
Since both metabolic and myogenic regulatory factors modulate blood flow, it is possible that concomitant alterations in shear stress may modify the overall microvascular response. In the case of the myogenic response, endothelial-derived factors do not appear to play a role, since denudation of the endothelium has no affect on the myogenic constriction of mesenteric vessels induced by an increase in intraluminal pressure . However, in vivo increases in perfusion pressure and blood flow would result in a situation where flow-mediated vasodilation would oppose myogenic-mediated vasoconstriction . In the case of the metabolic-mediated vasoregulation, endothelial-derived NO may either antagonize or potentiate the vascular responses to perturbations in O2 demand or delivery. For example, the intestinal hyperemia induced by an increase in O2 demand (e.g., nutrient transport) may be initiated by an NO-independent mechanism (e.g., tissue pO2, adenosine) and result in shear stress-induced, NO-dependent potentiation/prolongation of the hyperemia. By contrast, the intestinal vasodilation induced by reductions in O2 delivery (e.g., decreases in blood flow) may be antagonized by NO . Interestingly, mathematical modeling approaches based on experimental data predict that the combined influence of metabolic and myogenic mechanisms override the effects of shear stress in blood flow autoregulation .
Morgan & Claypool Life Sciences, San Rafael (CA)
Kvietys PR. The Gastrointestinal Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Chapter 3, Regulation of Vascular Tone and Oxygenation.