This study was designed to test the hypothesis that venular administration of ATP resulted in endothelium-dependent dilation of adjacent arterioles through a mechanism involving cyclooxygenase products. Forty-three male golden hamsters were anesthetized with pentobarbital sodium (60 mg/kg ip), and the cremaster muscle was prepared for in vivo microscopy. ATP (100 microM) injected into venules dilated adjacent arterioles from a mean diameter of 51 +/- 4 to 76 +/- 6 microm (P < 0.05, n = 6). To remove the source of endothelial-derived relaxing factors, the venules were then perfused with air bubbles to disrupt the endothelium. Resting arteriolar diameter was not altered after disruption of the venular endothelium (51 +/- 5 microm), and the responses to venular ATP infusions were significantly attenuated (59 +/- 4 microm, P < 0.05). To determine whether the relaxing factor was a cyclooxygenase product, ATP infusion studies were repeated in the absence and presence of indomethacin (28 microM). Under control conditions, ATP (100 microM) infusion into the venule caused an increase in mean arteriolar diameter from 55 +/- 4 to 78 +/- 3 microm (P < 0.05, n = 6). In the presence of indomethacin, mean resting arteriolar tone was not significantly altered (49 +/- 4 microm), and the response to ATP was significantly attenuated (54 +/- 4 microm, P < 0.05, n = 6). These studies show that increases in venular ATP concentrations stimulate the release of cyclooxygenase products, possibly from the venular endothelium, to vasodilate the adjacent arteriole.

Abstract-Indomethacin or glibenclamide treatments attenuate functional dilation of larger-diameter "feed" arterioles paired with venules in hamster cremaster muscle. We tested the hypothesis that release of cyclooxygenase products from venules is important for functional dilation of third-and fourth-order arterioles. We also tested whether ATP-sensitive potassium channels are important during functional dilation of smaller arterioles. The microcirculation of hamster cremaster muscle was visualized with in vivo video microscopy. We measured diameter responses of third-and fourth-order arterioles paired and unpaired with venules in response to 2 minutes of muscle field stimulation (40 s, 10 V, 1 Hz). Control diameters of vessels were 31Ϯ2 (nϭ19), 13Ϯ1 (nϭ12), 12Ϯ2 (nϭ12), and 10Ϯ1 (nϭ12) for paired and unpaired third-order and paired and unpaired fourth-order arterioles, respectively. In all groups, field stimulation resulted in increases in mean control diameter of Ͼ80%. Indomethacin (28 mol/L) superfused on the preparation was used to inhibit cyclooxygenase metabolism, or glibenclamide (10 mol/L) was used to block ATP-sensitive potassium channels. Indomethacin attenuated arteriolar vasodilations to electrical stimulation in paired third-order vessels only, whereas glibenclamide attenuated this vasodilation in all 4 groups. These results support a role for ATP-sensitive potassium channels in functional dilation of arterioles of all sizes regardless of whether or not they are paired with venules. Conversely, a role for cyclooxygenase products is limited to larger "feed arterioles" paired with venules. This study provides further evidence that venules may be the source of prostaglandin release during functional hyperemia. Key Words: indomethacin Ⅲ microcirculation Ⅲ arterioles Ⅲ potassium channels Ⅲ cyclooxygenase O ne of the remarkable characteristics of the microcirculation is the ability of the tissue to "control" local blood flow in such a manner that the metabolic requirements of the tissue are adequately met. For instance, during periods of increased muscle metabolism such as during exercise, blood flow to skeletal muscle increases. In hamster cremaster muscle, functional dilation of larger "feed" arterioles can be attenuated by disruption of the endothelium of venules running parallel to these arterioles, 1 by inhibition of ATPsensitive potassium (K ATP ) channels, 2 and by inhibiting the production of arachidonic acid metabolites. 3,4 Collectively, these studies suggest that during periods of increased muscle metabolism, a metabolite of arachidonic acid is released from the venular endothelium that subsequently diffuses to and dilates the adjacent arteriole.To achieve a maximal increase in blood flow to the tissue, all arterioles within the vascular tree must dilate. As vessels approach the capillary bed, they tend to lose their paired arrangement with venules, and in hamster cremaster muscle, many third-order and the majority of fourth-order arterioles do not have an adjacent venule (see Figure 1). Therefo...

Arachidonic acid (AA) is the common precursor for several vasodilatory factors involved in the local control of blood flow. This study was designed to determine the role of phospholipase A2(PLA2) and AA release in functional hyperemia in the hamster cremaster muscle. The muscle was prepared for in vivo microscopy and subjected to electrical field stimulation for 1 min. First- and second-order arterioles dilated in response from a mean diameter of 66 ± 5 to 88 ± 7 μm ( n = 6). PLA2 was then inhibited with quinacrine (3 × 10−6M) for 60 min. PLA2 inhibition was verified by an attenuation of thrombin-induced vasodilation (2 U/ml). Quinacrine had no effect on resting arteriolar diameter but completely abolished functional hyperemia. Quinacrine also had no effect on dilation induced by superfusion of the preparation with 3 × 10−6–10−5M AA, 10−6–10−4M adenosine, or 10−6–10−4M sodium nitroprusside, ruling out nonspecific effects of quinacrine on smooth muscle contractility. These results indicate that functional hyperemia in the hamster cremaster muscle is dependent on PLA2 activation and the availability of AA.