Endothelium-derived prostaglandin H2 evokes the stretch-induced contraction of rabbit pulmonary artery.

Stretch-induced contraction of rabbit pulmonary artery depends on endothelium-derived vasoactive prostanoids. We investigated which prostanoid(s) was responsible for the stretch-induced contraction of the artery, and whether integrin was involved in this mechanotransduction process. Stretch increased productions of untransformed prostaglandin H(2), prostaglandin E(2), prostaglandin F(2alpha), and thromboxane A(2) in the pulmonary artery with intact endothelium. A blocking peptide for integrins (RGD peptide) significantly inhibited productions of thromboxane A(2) and prostaglandin F(2alpha), but the peptide did not affect productions of untransformed prostaglandin H(2) and prostaglandin E(2), as well as contraction in response to stretch. SQ29,548, a prostaglandin H(2)/thromboxane A(2) receptor antagonist, inhibited the contractile response to not only stretch but also exogenous prostaglandin H(2). Acetylcholine (up to 30 microM) also contracted the artery in an endothelium-dependent manner. Ozagrel (10 nM-1 microM), an inhibitor of thromboxane synthase, abolished the production of thromboxane A(2), in response to both stretch and acetylcholine, whereas the inhibitor mostly inhibited acetylcholine-induced contraction, but it did not suppress stretch-induced contraction. The results suggested that prostaglandin H(2) and thromboxane A(2), either released from endothelium by mechanical stretch or by acetylcholine, produced contraction of rabbit pulmonary artery in a RGD-independent manner.