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K A Dora

Publications and source records attributed to K A Dora.

At least 19 recordsLinked to original sources
PubMed2003

Small- and intermediate-conductance calcium-activated K+ channels provide different facets of endothelium-dependent hyperpolarization in rat mesenteric artery.

Activation of both small-conductance (SKCa) and intermediate-conductance (IKCa) Ca2+-activated K+ channels in endothelial cells leads to vascular smooth muscle hyperpolarization and relaxation in rat mesenteric arteries. The contribution that each endothelial K+ channel type makes to the smooth muscle hyperpolarization is unknown. In the presence of a nitric oxide (NO) synthase inhibitor, ACh evoked endothelium and concentration-dependent smooth muscle hyperpolarization, increasing the resting potential (approx. -53 mV) by around 20 mV at 3 microM. Similar hyperpolarization was evoked with cyclopiazonic acid (10 microM, an inhibitor of sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA)) while 1-EBIO (300 microM, an IKCa activator) only increased the potential by a few millivolts. Hyperpolarization in response to either ACh or CPA was abolished with apamin (50 nM, an SKCa blocker) but was unaltered by 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (1 microM TRAM-34, an IKCa blocker). During depolarization and contraction in response to phenylephrine (PE), ACh still increased the membrane potential to around -70 mV, but with apamin present the membrane potential only increased just beyond the original resting potential (circa -58 mV). TRAM-34 alone did not affect hyperpolarization to ACh but, in combination with apamin, ACh-evoked hyperpolarization was completely abolished. These data suggest that true endothelium-dependent hyperpolarization of smooth muscle cells in response to ACh is attributable to SKCa channels, whereas IKCa channels play an important role during the ACh-mediated repolarization phase only observed following depolarization.

Animals↗
PubMed2003

A mechanosensitive cation channel in endothelial cells and its role in vasoregulation.

Ca2+ is an important intracellular second messenger in signal transduction of endothelial cells. It has long been recognized that a mechanosensitive Ca2+-permeable channel is present in vascular endothelial cells. The activity of this channel may increase intracellular Ca2+ level in endothelial cells. A recent finding is that the activity of this channel may be regulated by cGMP through a protein kinase G-dependent pathway. Inhibition of the channel by cGMP abolishes the Ca2+ influx elicited by flow. Several inhibitors of the cation channel including Gd3+, Ni2+, and SK&F-96365 also inhibit the Ca2+ influx due to flow stimulation. These data suggest that a mechanosensitive cation channel is the primary pathway mediating the flow-induced Ca2+ entry in vascular endothelial cells. Another important finding is that the opening of this mechanosensitive channel by KT5823 leads to endothelium-dependent vascular dilation. Therefore, it appears that this channel may play a crucial role in the regulation of vascular tone.

Animals↗
PubMed2001

Intercellular Ca2+ signalling: the artery wall.

The fact that many cells in the cardiovascular system are coupled via gap junctions enables direct intercellular Ca2+ signalling. Ca2+ ions and/or inositol trisphosphate (IP3) can pass through these aqueous pores. Cell-cell coupling can occur between cells of the same type, or via special junctions between adjacent cells of different types. Homocellular coupling acts to amplify and prolong Ca2+ signals, whereas heterocellular coupling allows complex interactions between the cells, including the modulation of their respective responses. This review will focus on the interactions between cells that form the blood vessel wall, illustrating how cell-cell communication defines important physiological functions.

Animals↗
PubMed2001

Activation of endothelial cell IK(Ca) with 1-ethyl-2-benzimidazolinone evokes smooth muscle hyperpolarization in rat isolated mesenteric artery.

1. In rat small mesenteric arteries contracted with phenylephrine, 1-ethyl-2-benzimidazolinone (1-EBIO; 3-300 microM) evoked concentration-dependent relaxation that, above 100 microM, was associated with smooth muscle hyperpolarization. 2. 1-EBIO-evoked hyperpolarization (maximum 22.1+/-3.6 mV with 300 microM, n=4) was endothelium-dependent and inhibited by charybdotoxin (ChTX 100 nM; n=4) but not iberiotoxin (IbTX 100 nM; n=4). 3. In endothelium-intact arteries, smooth muscle relaxation to 1-EBIO was not altered by either of the potassium channel blockers ChTX (100 nM; n=7), or IbTX (100 nM; n=4), or raised extracellular K(+) (25 mM). Removal of the endothelium shifted the relaxation curve to the right but did not reduce the maximum relaxation. 4. In freshly isolated mesenteric endothelial cells, 1-EBIO (600 microM) evoked a ChTX-sensitive outward K-current. In contrast, 1-EBIO had no effect on smooth muscle cell conductance whereas NS 1619 (33 microM) stimulated an outward current while having no effect on the endothelial cells. 5. These data show that with concentrations greater than 100 microM, 1-EBIO selectively activates outward current in endothelial cells, which presumably underlies the smooth muscle hyperpolarization and a component of the relaxation. Sensitivity to block with charybdotoxin but not iberiotoxin indicates this current is due to activation of IK(Ca). However, 1-EBIO can also relax the smooth muscle by an undefined mechanism, independent of any change in membrane potential.

Animals↗
PubMed2001

Endothelial cell protein kinase G inhibits release of EDHF through a PKG-sensitive cation channel.

The release of dilator agents from vascular endothelial cells is modulated by changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)). In this study, we demonstrate the presence of a Ca(2+)-permeable cation channel in inside-out membrane patches of endothelial cells isolated from small mesenteric arteries. The activity of the channel is increased by KT-5823, a highly selective inhibitor of protein kinase G (PKG), while it is decreased by direct application of active PKG. Application of KT-5823 induces Ca(2+) influx in the endothelial cells isolated from small mesenteric arteries, and it also causes endothelium-dependent relaxations in isolated small mesenteric arteries. KT-5823-induced relaxations in small mesenteric arteries are greatly reduced by 35 mM K(+) or 50 nM charybdotoxin + 50 nM apamin, suggesting that endothelium-derived hyperpolarizing factor (EDHF) is the participating dilator. The involvement of EDHF is further supported by experiments in which the relaxations of small mesenteric arteries are shown to be accompanied by membrane repolarization. These data strongly argue for a major role of a PKG-sensitive cation channel in modulating the release of EDHF from endothelial cells in rat small mesenteric arteries.

Acetylcholine↗
PubMed2001

Properties of smooth muscle hyperpolarization and relaxation to K+ in the rat isolated mesenteric artery.

Smooth muscle membrane potential and tension in rat isolated small mesenteric arteries (inner diameter 100-200 microm) were measured simultaneously to investigate whether the intensity of smooth muscle stimulation and the endothelium influence responses to exogenous K+. Variable smooth muscle depolarization and contraction were stimulated by titration with 0.1-10 microM phenylephrine. Raising external K+ to 10.8 mM evoked correlated, sustained hyperpolarization and relaxation, both of which were inhibited as the smooth muscle depolarized and contracted to around -38 mV and 10 mN, respectively. At these higher levels of stimulation, raising the K+ concentration to 13.8 mM still hyperpolarized and relaxed the smooth muscle. Relaxation to endothelium-derived hyperpolarizing factor, released by ACh, was not altered by the level of stimulation. In endothelium-denuded arteries, the concentration-relaxation curve to K+ was shifted to the right but was not depressed. In denuded arteries, relaxation to K+ was unaffected by the extent of prior stimulation and was blocked with 0.1 mM ouabain but not with 30 microM Ba2+. The ability of K+ to stimulate simultaneous hyperpolarization and relaxation in the mesenteric artery is consistent with a role as an endothelium-derived hyperpolarizing factor activating inwardly rectifying K+ channels on the endothelium and Na+-K+-ATPase on the smooth muscle cells.

Acetylcholine↗
PubMed2001

Cell-cell communication in the vessel wall.

Intercellular communication between cells within the blood vessel wall plays an important role in the control of artery diameter. The endothelial cells lining the lumen of arteries can evoke smooth muscle hyperpolarization both by the release of a factor (EDHF) and by direct cell-cell coupling through gap junctions. Hyperpolarizing current can spread rapidly to cause widespread vasodilatation, and thus increase blood flow to that segment. In addition to the spread of current, small molecules, such as Ca2+, can also pass between cells, but at a much reduced rate. Instead of co-ordinating changes in diameter, intercellular Ca2+ signalling acts to amplify and, in special cases, modulate vascular responses. Together, direct cell-cell communication enables the blood vessel wall to act as a functional syncytium, which is influenced by surrounding tissues and nerves, and blood constituents.

Animals↗
PubMed2000

An indirect influence of phenylephrine on the release of endothelium-derived vasodilators in rat small mesenteric artery.

1. The possibility that stimulation of smooth muscle alpha(1)-adrenoceptors modulates contraction via the endothelium was examined in rat small mesenteric arteries. 2. N(omega)-nitro-L-arginine methyl ester, (L-NAME, 100 microM to inhibit NO synthase) increased contraction to single concentrations of phenylephrine (1 - 3 microM) by approximately 2 fold (from a control level of 14.2+/-3.0 to 34. 1+/-4.2% of the maximum contraction of the artery, n=20). The action of L-NAME was abolished by disrupting the endothelium. 3. The subsequent addition of apamin (to inhibit small conductance Ca(2+)-activated K(+) channels, 50 nM) further augmented phenylephrine contractions, in an endothelium-dependent manner, to more than 3 fold above control (50.4+/-5.3% of the maximum contraction, n=11). 4.Charybdotoxin (non-selective inhibitor of large conductance Ca(2+)-activated K(+) channels, BK(Ca), 50 nM) plus L-NAME augmented the level of phenylephrine contraction to 4 - 5-fold above control (64.1+/-3.1%, n=5), but this effect was independent of the endothelium. The potentiation of contraction by charybdotoxin could be mimicked with the selective BK(Ca) inhibitor, iberiotoxin,. 5. Apamin together with L-NAME and charybdotoxin further significantly increased the phenylephrine contraction by 5 - 6-fold, to 79.9+/-3.5% of the maximum contraction of the artery (n=13). 6. Phenylephrine failed directly to increase the intracellular Ca(2+) concentration in endothelial cells freshly isolated from the small mesenteric artery. 7. Stimulation of smooth muscle alpha(1)-adrenoceptors in the mesenteric artery induces contraction that is markedly suppressed by the endothelium. The attenuation of contraction appears to reflect both the release of NO from the endothelium and the efflux of K(+) from both endothelial and smooth muscle cells. This suggests that the release of NO and endothelium-derived hyperpolarizing factor can be evoked indirectly by agents which act only on the smooth muscle cells.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2000

The involvement of intracellular Ca(2+) in 5-HT(1B/1D) receptor-mediated contraction of the rabbit isolated renal artery.

5-Hydroxytryptamine(1B/1D) (5-HT(1B/1D)) receptor coupling to contraction was investigated in endothelium-denuded rabbit isolated renal arteries, by simultaneously measuring tension and intracellular [Ca(2+)], and tension in permeabilized smooth muscle cells. In intact arterial segments, 1 nM - 10 microM 5-HT failed to induce contraction or increase the fura-2 fluorescence ratio (in the presence of 1 microM ketanserin and prazosin to block 5-HT(2) and alpha(1)-adrenergic receptors, respectively). However, in vessels pre-exposed to either 20 mM K(+) or 30 nM U46619, 5-HT stimulated concentration-dependent increases in both tension and intracellular [Ca(2+)]. 1 nM - 10 microM U46619 induced concentration-dependent contractions. In the presence of nifedipine (0.3 and 1 microM) the maximal contraction to U46619 (10 microM) was reduced by around 70%. The residual contraction was abolished by the putative receptor operated channel inhibitor, SKF 96365 (2 microM). With 0.3 microM nifedipine present, 100 nM U46619 evoked similar contraction to 30 nM U46619 in the absence of nifedipine, but contraction to 5-HT (1 nM - 10 microM) was abolished. In permeabilized arterial segments, 10 mM caffeine, 1 microM IP(3) or 100 microM phenylephrine, each evoked transient contractions by releasing Ca(2+) from intracellular stores, whereas 5-HT had no effect. In intact arterial segments pre-stimulated with 20 mM K(+), 5-HT-evoked contractions were unaffected by 1 microM thapsigargin, which inhibits sarco- and endoplasmic reticulum calcium-ATPases. In vessels permeabilized with alpha-toxin and then pre-contracted with Ca(2+) and GTP, 5-HT evoked further contraction, reflecting increased myofilament Ca(2+)-sensitivity. Contraction linked to 5-HT(1B/1D) receptor stimulation in the rabbit renal artery can be explained by an influx of external Ca(2+) through voltage-dependent Ca(2+) channels and sensitization of the contractile myofilaments to existing levels of Ca(2+), with no release of Ca(2+) from intracellular stores.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Microvascular dilation in response to occlusion: a coordinating role for conducted vasomotor responses.

In rat cremasteric microcirculation, mechanical occlusion of one branch of an arteriolar bifurcation causes an increase in flow and vasodilation of the unoccluded daughter branch. This dilation has been attributed to the operation of a shear stress-dependent mechanism in the microcirculation. Instead of or in addition to this, we hypothesized that the dilation observed during occlusion is the result of a conducted signal originating distal to the occlusion. To test this hypothesis, we blocked the ascending spread of conducted vasomotor responses by damaging the smooth muscle and endothelial cells in a 200-microm segment of second- or third-order arterioles. We found that a conduction blockade eliminated or diminished the occlusion-associated increase in flow through the unoccluded branch and abolished or strongly attenuated the vasodilatory response in both vessels at the branch. We also noted that vasodilations induced by ACh (10(-4) M, 0.6 s) spread to, but not beyond, the area of damage. Taken together, these data provide strong evidence that conducted vasomotor responses have an important role in coordinating blood flow in response to an arteriolar occlusion.

Acetylcholine↗
PubMed1999

Role of heterocellular Gap junctional communication in endothelium-dependent smooth muscle hyperpolarization: inhibition by a connexin-mimetic peptide.

A synthetic connexin-mimetic peptide (Gap 27 peptide) was used to evaluate the contribution of gap junctional communication to smooth muscle responses mediated by the endothelium-dependent agonist acetylcholine (ACh) in rabbit mesenteric arteries. Hyperpolarizations and relaxations to 0.1 and 1 microM ACh observed in the presence of nitric oxide synthase and cyclooxygenase inhibition were markedly attenuated by the peptide at a concentration of 300 microM, whereas the hyperpolarizing response to levcromakalim, a KATP channel opener, was unaffected. The peptide also attenuated intercellular transfer of Lucifer yellow in confluent cultures of COS-7 cells, thus confirming its ability to modulate the permeability of gap junctions. The findings demonstrate that heterocellular gap junctional communication contributes to NO- and prostanoid-independent mechanisms of vasorelaxation that are widely attributed to an endothelium-derived hyperpolarizing factor.

Animals↗
PubMed1998

K+ is an endothelium-derived hyperpolarizing factor in rat arteries.

In arteries, muscarinic agonists such as acetylcholine release an unidentified, endothelium-derived hyperpolarizing factor (EDHF) which is neither prostacyclin nor nitric oxide. Here we show that EDHF-induced hyperpolarization of smooth muscle and relaxation of small resistance arteries are inhibited by ouabain plus Ba2+; ouabain is a blocker of Na+/K+ ATPase and Ba2+ blocks inwardly rectifying K+ channels. Small increases in the amount of extracellular K+ mimic these effects of EDHF in a ouabain- and Ba2+-sensitive, but endothelium-independent, manner. Acetylcholine hyperpolarizes endothelial cells and increases the K+ concentration in the myoendothelial space; these effects are abolished by charbdotoxin plus apamin. Hyperpolarization of smooth muscle by EDHF is also abolished by this toxin combination, but these toxins do not affect the hyperpolarizaiton of smooth muscle by added K+. These data show that EDHF is K+ that effluxes through charybdotoxin- and apamin-sensitive K+ channels on endothelial cells. The resulting increase in myoendothelial K+ concentration hyperpolarizes and relaxes adjacent smooth-muscle cells by activating Ba2+-sensitive K+ channels and Na+/K+ ATPase. These results show that fluctuations in K+ levels originating within the blood vessel itself are important in regulating mammalian blood pressure and flow.

Acetylcholine↗
PubMed1997

Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles.

It is well known that vascular smooth muscle tone can be modulated by signals arising in the endothelium (e.g., endothelium-derived relaxing factor, endothelium-derived hyperpolarizing factor, and prostaglandins). Here we show that during vasoconstriction a signal can originate in smooth muscle cells and act on the endothelium to cause synthesis of endothelium-derived relaxing factor. We studied responses to two vasoconstrictors (phenylephrine and KCl) that act by initiating a rise in smooth muscle cell intracellular Ca2+ concentration ([Ca2+]i) and exert little or no direct effect on the endothelium. Fluo-3 was used as a Ca2+ indicator in either smooth muscle or endothelial cells of arterioles from the hamster cheek pouch. Phenylephrine and KCl caused the expected rise in smooth muscle cell [Ca2+]i that was accompanied by an elevation in endothelial cell [Ca2+]i. The rise in endothelial cell [Ca2+]i was followed by increased synthesis of NO, as evidenced by an enhancement of the vasoconstriction induced by both agents after blockade of NO synthesis. The molecule involved in signal transmission from smooth muscle to endothelium is as yet unknown. However, given that myoendothelial cell junctions are frequent in these vessels, we hypothesize that the rise in smooth muscle cell Ca2+ generates a diffusion gradient that drives Ca2+ through myoendothelial cell junctions and into the endothelial cells, thereby initiating the synthesis of NO.

Acetylcholine↗
PubMed1997

Serotonin inhibition of 1-methylxanthine metabolism parallels its vasoconstrictor activity and inhibition of oxygen uptake in perfused rat hindlimb.

The effect of serotonin (5-HT) on the metabolism of infused 1-methylxanthine (1-MX), a putative substrate of capillary endothelial xanthine oxidase (XO), and on the distribution of infused fluorescent microspheres (15 microns) by the artificially constant-flow perfused rat hindlimb preparation was investigated. 1-MX (5-100 microM) caused a slight inhibition of oxygen uptake (Vo2) but was not vasoactive, either alone or with 5-HT. 1-MX was converted to 1-methylurate (1-MU) and this conversion was inhibited by allopurinol and xanthine. 5-HT (0.35 microM), which caused vasoconstriction and decreased Vo2, also inhibited the conversion of 1-MX, indicated by a lowered venous perfusate steady-state 1-MU:1-MX ratio from 1.14 +/- 0.02 to 0.71 +/- 0.02 (P < 0.001), which is equivalent to the rate of conversion decreasing from 0.83 +/- 0.03 to 0.63 +/- 0.05 nmol min-1 g-1. This change closely followed the time course for changes in Vo2 and perfusion pressure and all three changes reversed in parallel when 5-HT was removed. Recoveries of 1-MU plus 1-MX at all times were high (100 +/- 5%). 5-HT did not act to inhibit XO. When compared with vehicle alone, 5-HT had either no effect (plantairs, gastrocnemius white, tibialis, extensor digitorum longus, vastus and thigh), or increased microsphere content (soleus and gastrocnemius red, P < 0.05) of muscles with only bone showing a significant decrease (P < 0.05). Since 5-HT did not inhibit XO or alter the net flow to individual muscles in this constant-flow model, the inhibition of conversion of 1-MX to 1-MU is concluded to be the result of a 5-HT-mediated decrease in the access of 1-MX to capillary XO within individual muscles. Possibilities include the redirection of flow to capillaries either in muscle or in connective tissue closely associated with muscle, where resistance is low and effective surface area is less. 1-MX has potential as a marker for muscle nutritive flow.

Animals↗
PubMed1997

A test of the role of flow-dependent dilation in arteriolar responses to occlusion.

At an arteriolar bifurcation, occlusion of one of the branch arterioles has been reported to result in an increase in flow, shear stress, and vasodilation in the opposite unoccluded branch. This dilator response in the unoccluded branch, often referred to as the "parallel occlusion response," has been cited as evidence that flow-dependent dilation is a primary regulator of arteriolar diameter in the microcirculation. It has not been previously noted that, during this maneuver, flow through the feed arteriole would be expected to decrease and logically should cause that vessel to constrict. We tested this prediction in vivo by measuring red blood cell (RBC) velocity and diameter changes in response to arteriolar occlusion in the microcirculatory beds of three preparations: the hamster cheek pouch, the hamster cremaster, and the rat cremaster. In all preparations, a vasodilation was observed in the feed arteriole, despite a decrease in both flow and calculated wall shear stress through this vessel. Unexpectedly, we found that dilation occurred in the unoccluded branch arterioles even in those cases in which RBC velocity and shear stress did not increase in the unoccluded branch arterioles. All values returned to the baseline level after the removal of occlusion. The magnitude of the dilation of the feed and branch arterioles varied between species and tissues, but feed and branch arterioles within a given preparation always responded in a similar way to each other. We conclude from our experiments that mechanisms other than flow-dependent dilation are involved in the vasodilation observed in the microcirculation during occlusion of an arteriolar branch.

Animals↗
PubMed1997

Vasoconstrictor-mediated increase in muscle resting thermogenesis is inhibited by membrane-stabilizing agents.

Norepinephrine and angiotensin II are potent vasoconstrictors and stimulate thermogenesis (oxygen uptake) as well as lactate and glycerol efflux in the constant-flow perfused rat hind limb at rest. However, the mechanism by which oxygen uptake (VO2) is increased is unknown, and it is not clear whether vasoconstriction is required for the increase in VO2 by the hind limb. In the present study the association between vasoconstriction and VO2 was further investigated, and a chance observation that high-dose propranolol selectively blocked vasoconstrictor-induced increase in VO2 was further explored. The norepinephrine-mediated increase in VO2 was totally blocked by either 50 microM (+)-propranolol or 50 microM (-)-propranolol (active beta-blocking enantiomer), but only (+)-propranolol reduced the vasoconstriction. Similarly, 100 microM (+/-)-propranolol (a dose likely to cause plasma membrane stabilizing effects involving interruption and (or) prevention of action potentials) blocked increases in VO2, lactate, and glycerol efflux by 5 nM angiotensin II (a nonadrenergic vasoconstrictor) with only marginal effects on pressure development. (+/-)-Propranolol (100 microM) had no effect on postequilibration red blood cell washout mediated by angiotensin II, a putative indicator of vasoconstrictor-induced redistribution of flow. Quinidine (260 microM) (an antiarrhythmic agent with membrane-stabilizing activity) inhibited only the increase in VO2, but neither nadolol (300 microM) nor atenolol (300 microM) (beta-blockers without membrane-stabilizing activity) inhibited VO2 or perfusion pressure increases produced by 5 nM angiotensin II. Veratridine (a membrane labilizer that is capable of evoking plasma membrane depolarization by maintaining voltage-gated Na+ channels in their open state) increased VO2 without vasoconstriction, and the increase in VO2 was blocked by 100 microM (+/-)-propranolol. It is concluded that the increase in hind-limb VO2 results from a destabilization of skeletal muscle plasma membranes. This can be achieved directly by veratridine or indirectly by angiotensin II, involving vasoconstriction and redistribution of flow. The findings suggest a novel mechanism for resting muscle thermogenesis.

Adrenergic beta-Antagonists↗
PubMed1996

Norepinephrine and serotonin vasoconstriction in rat hindlimb control different vascular flow routes.

The vasoconstrictors, norepinephrine at low dose ( < or = 0.1 microM; LDNE) and serotonin (5-HT), produce opposing metabolic effects in the constant-flow perfused rat hindlimb characterized by increased and decreased oxygen uptake, respectively. In the present study, the effects of each vasoconstrictor are compared in the red blood cell-free buffer-perfused hindlimb on postequilibration endogenous red blood cell efflux, vascular entrapment of fluorescein-labeled dextran (Fx), and vascular corrosion casting by use of 30-micron spheres of methyl methacrylate (MM). A marked transient washout of red blood cells occurred immediately in association with vasoconstriction induced by LDNE that was not apparent when a similar extent of vasoconstriction was induced by 5-HT. Fx perfusions indicated that LDNE recruited a new vascular space that was reaccessed by a second exposure to the vasoconstrictor. 5-HT closed off a previously perfused vascular space that was reaccessed when the vasoconstrictor was removed. Corrosion casting of the arterial tree with MM showed no increase in cast weight, but more vessels filled because of LDNE. Higher doses of NE (2.5 microM) or 5-HT caused a marked decrease in cast weight with fewer vessels filled. The data suggest that LDNE and 5-HT, in association with vasoconstriction at different sites, control different capillary flow routes in the hindlimb that in turn may influence metabolism by increasing or decreasing nutrient access, respectively.

Animals↗