The importance of endogenous prostaglandins other than prostacyclin, for the modulation of contractility of some rabbit blood vessels

Abstract

1 Helically cut strips of rabbit aorta, extrapulmonary artery, coeliac artery, and femoral artery were set up in organ baths. Contractions of the strips by noradrenaline and angiotensin II were recorded isotonically. The release of prostaglandins 6-keto-PGF1,, E2, F2X, D2 and thromboxane B2 from the strips was measured by means of sensitive and specific radioimmunoassays. 2 All blood vessels released a characteristic pattern of cyclo-oxygenase products. Prostacyclin (PGI2, measured as 6-keto-PGF1a) was the major compound formed, followed by smaller amounts of PGE2 and traces of PGF2a, PGD2 and thromboxane A2 (measured as thromboxane B2). The pulmonary and the femoral artery had comparatively high abilities to synthesize PGE2. 3 Contractions induced by noradrenaline increased prostaglandin release from the pulmonary artery but not from the other blood vessels. Angiotensin II-induced contractions were accompanied by a marked prostaglandin release from the coeliac artery. After angiotensin II, prostaglandin release was also enhanced in the pulmonary artery, but remained essentially unchanged in the aorta and femoral artery. 4 Arachidonic acid markedly increased the levels of all prostaglandin formed. 5 Indomethacin inhibited the formation of all prostaglandins below the detection limits of the respective radioimmunoassays. 6 Indomethacin treatment induced a qualitatively similar shifting of the concentration-response curves of noradrenaline and angiotensin II in some vessels: the concentration-response curves remained unchanged for the aorta, were slightly shifted to the left of the pulmonary artery, were markedly shifted to the left for the coeliac artery, and were shifted to the right for the femoral artery. 7 Exogenous PGI2 strongly and concentration-dependently inhibited contractions induced by the approximate EC50 of noradrenaline in the coeliac artery, but was without effect on the other three preparations. PGE2 had no effect on noradrenaline-induced contractions of the aorta, inhibited those of the pulmonary and the coeliac artery, but markedly potentiated those of the femoral artery. PGF2: significantly enhanced contractions of the femoral artery, but increased contractions of the other preparations were not significant. PGD2 was without effect on any preparation. 8 In conclusion, the contractility of the aorta does not seem to be modulated substantially by prostaglandins. The major prostanoid regulating the tone of the coeliac artery was found to be PGI2. The contractility of the pulmonary and especially the femoral artery is probably not modulated by PGI2 but rather by PGE2. 9 These observations suggest that in certain blood vessels, prostaglandins other than PGI2 are important endogenous modulators of contractility.

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

“…Our results do not exclude a possible role for prostaglandins in metabolic and ischemic vasodilation of the cutaneous microcirculation. Furthermore, the role of prostaglandins in endothelium-mediated vasodilation varies among species and among vascular beds within species (14,24,35). Finally, we cannot exclude a role for prostaglandins in endothelium-mediated vasodilation in other vascular beds.…”

Vascular mode of action of kinin B1 receptors and development of a cellular model for the investigation of these receptors

“…It is possible that the increased PGI2 production is a uniform response of large rabbit vessels to B, receptor stimulation, but that the local sensitivity to prostanoids varies from one preparation to another. Indeed, the rabbit aorta does not exhibit a relaxant response to PGI2 or PGE2, the major eicosanoids produced by rabbit isolated vessels under basal or stimulated conditions (Forstermann et al, 1984). On the contrary, the mesenteric and coeliac arteries are relaxed by low concentrations of these prostaglandins (Simmet & Hertting, 1980;Forstermann et al, 1984;Demirel & Tiirker, 1991) IL-lpl (-20h) IL-I p (-20h) IL-lp (-20h) IL-lp (-20h) IL-I p (-20h) IL-1Ip (-20 onists confirmed the receptor identity (Figure 4, Table 3).…”

“…The inhibitory drugs under study were nifedipine, an L-type Ca2" channel blocker (Murad, 1990), the protein kinase inhibitors H-7 and H-9 (Hidata et al, 1984), indomethacin, the 5-lipoxygenase blocker (REV-5901 (McMillan & Walker, 1992) and the guanylyl cyclase inhibitory LY-83583 (Mulsch et al, 1989 In some experiments, the possible stimulation of eicosanoid release by des-Arg9-BK was tested by measuring the concentration of 6-keto-prostaglandin Fl,r (6-keto-PGF1,), the major cyclo-oxygenase product in this tissue (Forstermann et al, 1984), in the bathing fluid. Some tissues were exposed to indomethacin (2.8 JM) 30 min before the effect of des-Arg9-BK was examined.…”

“…The inhibitor of the soluble form of guanylyl cyclase, LY-83583, also failed to inhibit the contractile effect of any of the two stimuli at a concentration that reportedly inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in the acetylcholine-stimulated rabbit aorta (Diamond, 1987). The major eicosanoid produced by the isolated aorta, either in the basal or stimulated conditions is PGI2 (Forstermann et al, 1984). We have measured the concentration of immunoreactive 6-keto-PGF1,, the PGI2 breakdown product, in the bathing fluid of rabbit aortic rings challenged with des-Arg9-BK (Table 2).…”

Individual variations of prostanoid agonist responses in rabbit aorta: evidence for the independent regulation of prostanoid receptor subtypes

“…The rabbit aorta exhibits a relatively greater sensitivity effects of PGE2 and PGI2 (Bunting et al, 1976b; to the contractile effects of the prostaglandin Forstermann et al, 1984). These properties enabled e~idoperoxides, prostaglandin G2 (PGG2) and PGH2, Piper & Vane (1969) to characterize rabbit aorta and to thromboxane A2 (TxA2) than to other proscontracting substance (RCS) as an unstable biological taglandins (Bunting et al, 1976a;Gryglewski et al, activity released during anaphylaxis in isolated lungs Coleman et al, 1980;Vane, 1983 (Hamberg et al, 1974;1975;Svensson et al, 1975;Needleman et al, 1976).…”