Differential inhibition of functional dilation of small arterioles by indomethacin and glibenclamide.

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 microseconds, 10 V, 1 Hz). Control diameters of vessels were 31+/-2 (n=19), 13+/-1 (n=12), 12+/-2 (n=12), and 10+/-1 (n=12) 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 >80%. Indomethacin (28 micromol/L) superfused on the preparation was used to inhibit cyclooxygenase metabolism, or glibenclamide (10 micromol/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.