Dilator NO, prostaglandins (PGs) and constrictor PGH2/thromboxane A2 mediate flow‐induced dilation of venules.

Abstract

Mediation of flow dependent responses of venules is still not well characterized. We hypothesized that nitric oxide (NO) and prostanoids contribute to the mediation of responses. Thus, changes in diameter of pressurized venules (active diam.: 259±11 μm, and passive diam.: 412±11 μm, at 10 mmHg) isolated from rat gracilis muscle to increases in perfusate flow were measured, before and after incubation of the vessels with the prostaglandin H2/thromboxane A2 (PGH2/TXA2) receptor blocker SQ 29,548, or the NO synthase inhibitor Nω‐nitro‐L‐arginine‐methyl‐esther (L‐NAME), or the non‐specific cyclooxygenase (COX‐1 and COX‐2) inhibitor indomethacin (INDO), or the specific COX‐1 inhibitor SC 560, or COX‐2 inhibitor NS 398, or with their combination. Increases in flow elicited dilations (max. ΔD: 18±3 %), which were significantly augmented in the presence of SQ 29,548 (37±3 %). Additional presence of L‐NAME, or INDO significantly decreased the dilations (max. ΔD: 23±4 and 15±5, respectively), whereas SC 560 significantly reduced the dilations (max. ΔD: 12±6 %), and NS 398 was without effect. Thus, in isolated skeletal muscle venules, the final response to increases in flow is dilation, due to the combined effect of dilator NO and COX‐1‐derived PGE2/PGI2 and constrictor PGH2/TXA2. We propose that flow‐induced release of dilator and constrictor mediators contribute to the regulation of peripheral venular resistance. (Grants: Hungarian Sci. Res. Funds/OTKA: T48376, T767984 and Health Sci. Council/ETT 364/2006; and Am. Heart Assoc. NE Aff. 0555897T, USA)