Differential Inhibition of Functional Dilation of Small Arterioles by Indomethacin and Glibenclamide

Hammer, Leah W.; Ligon, Alison L.; Hester, Robert L.

doi:10.1161/01.hyp.37.2.599

Cited by 33 publications

(45 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were also found in patients with type 2 diabetes (14). Because previous studies have supported a critical role of prostaglandin(s) in mediating functional vasodilation (10,19,20,24,30), it is possible that the impaired functional vasodilation in metabolic syndrome may be due to altered AA metabolism. Indeed, previous studies have shown that urinary thromboxane B 2 excretion is enhanced in 12-wk-old OZRs associated with an increased cyclooxygenase-2 expression in kidney (3,15).…”

Section: Discussionsupporting

confidence: 80%

“…Indeed, the role of NO in mediating functional vasodilation in humans and animals is still unclear. Our previous study showed that, in the cremaster muscle, inhibition of cyclooxygenase with indomethacin significantly attenuates functional dilation (19,24), suggesting that prostaglandins play a central role in functional hyperemia (10). Indeed, endothelial-derived prostacyclin (PGI 2 ) has been proposed as playing an important role in regulating local blood flow during exercise through activation of PGI 2 receptors prostacyclin (IP) on vascular smooth muscle cells (20,30).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome

Xiang¹,

Naik²,

Hodnett³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

Xiang, Lusha, Jay S. Naik, Benjamin L. Hodnett, and Robert L. Hester. Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 290: R134 -R138, 2006. First published September 15, 2005 doi:10.1152/ajpregu.00295.2005.-These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 M SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 M), arachidonic acid (10 M), and sodium nitroprusside (0.1, 1, and 10 M) in the absence or presence of 1 M SQ-29548. A 10 M concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 M SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 M) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation.obese Zucker rat; prostacyclin; thromboxane; vasoconstriction IT IS WELL ESTABLISHED THAT, during periods of increased skeletal muscle metabolism (such as during exercise), blood flow to the muscle increases (functional hyperemia) because of dilation of local arterioles (functional dilation), and this vasodilatory response is dependent, in some part, on endothelial function (22). However, in patients and animals with metabolic syndrome, endothelial dysfunction may occur early in the pathology of this syndrome (4), possibly contributing to the impaired functional hyperemia seen in metabolic syndrome. For example, patients with type 2 diabetes exhibit an impaired endothelial-dependent vasodilatory response to ACh and a significant impairment of the functional hyperemic response to leg cycle ergometer exercise (14). Our laboratory and others (8,32) have demonstrated that the obese Zucker rat (OZR), a model of metabolic syndrome, have both an attenuated functional and ACh-induced vasodilation in skeletal muscle arterioles. Although the mechanism(s) responsible for the impaired functional dilation remains unclear, these studies reveal a possible relationship between the endothelial dysfunction and the impaired functional vasodilation.The determination of the mechanism(s) responsible...

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome

Xiang¹,

Naik²,

Hodnett³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

show abstract

“…The authors speculate that these vessels are alternative drainage routes for the blood, which could prevent a rapid washout of the end products of myocardial metabolism, allowing for prolonged arterial vasodilation. In the hamster cremaster muscle, pairing usually persists down to the arterioles, which are two or three generations upstream from the capillaries (20,38). Depending on the nomenclature used to classify the arterioles of the microcirculation, these smaller paired vessels give rise to the transverse arterioles (38) or unpaired third-or fourth-order arterioles (20).…”

Section: Anatomical Evidence For Venular-arteriolar Communicationmentioning

confidence: 99%

“…In the hamster cremaster muscle, pairing usually persists down to the arterioles, which are two or three generations upstream from the capillaries (20,38). Depending on the nomenclature used to classify the arterioles of the microcirculation, these smaller paired vessels give rise to the transverse arterioles (38) or unpaired third-or fourth-order arterioles (20). As noted in the previous paragraph, arterioles upstream from the transverse arterioles provide the most resistance to blood flow within a vascular bed and it is these vessels that are tightly paired with venules.…”

Section: Anatomical Evidence For Venular-arteriolar Communicationmentioning

confidence: 99%

Venular-arteriolar communication in the regulation of blood flow

Hester

Hammer

2002

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

Hester, Robert L., and Leah W. Hammer. Venular-arteriolar communication in the regulation of blood flow. Am J Physiol Regulatory Integrative Comp Physiol 282: R1280-R1285, 2002; 10.1152/ajpregu. 00744.2001.-Muscle blood flow is regulated to meet the metabolic needs of the tissue. With the vasculature arranged as a successive branching of arterioles and the larger, Ͼ50 m, arterioles providing the major site of resistance, an increasing metabolic demand requires the vasodilation of the small arterioles first then the vasodilation of the more proximal, larger arterioles. The mechanism(s) for the coordination of this ascending vasodilation are not clear and may involve a conducted vasodilation and/or a flow-dependent response. The close arteriolar-venular pairing provides an additional mechanism by which the arteriolar diameter can be increased due to the diffusion of vasoactive substances from the venous blood. Evidence is presented that the venular endothelium releases a relaxing factor, a metabolite of arachidonic acid, that will vasodilate the adjacent arteriole. The stimulus for this release is not known, but it is hypothesized that hypoxia-induced ATP release from red blood cells may be responsible for the stimulation of arachidonic release from the venular endothelial cells. Thus the venous circulation is in an optimal position to monitor the overall metabolic state of the tissue and thus provide a feedback regulation of arteriolar diameter. vasodilation; venular endothelium; relaxing factor TISSUE BLOOD FLOW is regulated to meet the metabolic needs of each tissue and can change quite dramatically. Increases in tissue metabolism cause increases in blood flow (functional hyperemia), whereas excess oxygen delivery causes a decrease in blood flow. Blood flow to skeletal or cardiac muscle increases proportionally with increases in metabolic rate to ensure adequate delivery of nutrients and removal of waste products. Although the precise mechanisms governing this close relationship between metabolic state of the tissue and blood flow remain to be elucidated, the anatomical arrangement of arteries and veins may provide a unique mechanism allowing the exchange of information or "cross-talk" between the pre-and postcapillary vessels.The vasculature is arranged as a series of blood vessels ranging in size from several millimeters to several micrometers, with the largest contribution of total resistance to blood flow coming from the large "feed" arterioles. Thus, to achieve optimal increases in blood flow during periods of increased muscle metabolism, large decreases in resistance of these arterioles must occur. As these upstream or feed vessels are not necessarily in contact with the metabolically active tissue, mechanisms other than or in addition to direct stimulation by tissue metabolites must be important in functional hyperemia. Mechanisms that have been proposed to regulate the diameter of upstream vessels include 1) conducted vasodilation (14), 2) flow-dependent vasodilation (29), and 3) myogenic vasodilation ...

show abstract

“…An alternative explanation is that another mediator diffuses from venule to arteriole in the NO-dependent dilatory mechanism. Cyclooxygenase metabolites play a major role in venule-mediated arteriolar dilation in functional hyperemia, but possibly not in resting conditions (7). Adenosine is a potent vasodilator in many vascular beds, and adenosine release is increased during hypoxia, ischemia, or metabolic stress, when O 2 delivery is inadequate to meet the tissue demand (18,32).…”

mentioning

confidence: 99%

Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

Kim

2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Kim, Min-ho, and Norman R. Harris. Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide. Am J Physiol Heart Circ Physiol 291: H724 -H731, 2006. First published March 31, 2006 doi:10.1152/ajpheart.01215.2005.-Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 Ϯ 1.0 m) paired with venules with minimal leukocyte adherence (2.1 Ϯ 0.3 per 100-m length) was significantly larger than that of unpaired arterioles (24.5 Ϯ 0.8 m) and arterioles (23.3 Ϯ 1.3 m) paired with venules with higher leukocyte adherence (9.0 Ϯ 0.5 per 100-m length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10 Ϫ4 M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine-and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence. leukocyte adhesion; Tempol RESTING ARTERIOLAR TONE can be determined by various endogenous vasoactive substances, the release of which depends on the metabolic state of the tissue, as well as on hemodynamic factors such as shear stress and pressure. In addition, when an arteriole is closely paired with a venule, vasoactive substances released from the venule also play an important role in regulating arteriolar diameter, depending on various stimulated conditions such as an increase in venular shear rate (26), an increase in muscle stimulation (16), and an exogenous venular infusion of vasoactive substances (5, 11). Nitric oxide (NO), prostaglandins, and adenosine have been implicated as mediators of venule-induced arteriolar dilation. Anatomically, various sizes of arterioles from large to small are paired with venules within a short diffusion distance in most tissues, and this close arrangement enables venular-arteriolar diffusion of vasoactive substances.In this study, we hypothesized that endogenous adenosine induces venule-dependent dilation of closely paired arte...

show abstract

Differential Inhibition of Functional Dilation of Small Arterioles by Indomethacin and Glibenclamide

Cited by 33 publications

References 16 publications

Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome

Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome

Venular-arteriolar communication in the regulation of blood flow

Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

Contact Info

Product

Resources

About