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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.

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nomifensine (1, 10 gAM) reduced the tritium accumulation to 65% whereas 6-nitroquipazine (1 JM) was ineffective. The combination of both drugs (1 JAM each) led to a further decrease to about 15%.3 The uptake of [3H]-dopamine into hippocampal slices was blocked by both nomifensine (I JM) and 6-nitroquipazine (I ILM) whereas in caudate nucleus slices only nomifensine (1, 1OtM) reduced the accumulation of [3H]-dopamine. The combination of both drugs was not more effective than nomifensine alone. The different effects of both uptake inhibitors in the hippocampus and caudate nucleus suggest a neurone specific rather than a substrate specific mode of action. 4 In caudate nucleus slices incubated with [3H]-5-HT and superfused continuously the electrically evoked 5-HT release was diminished by the D2-dopamine receptor agonist LY 171555 and enhanced by the D2-receptor antagonist domperidone. If, however, the labelling of caudate nucleus slices was performed in the presence of I JAM or 1OJM nomifensine, the modulation of 5-HT release via D2-receptors was reduced or abolished, respectively. In the hippocampus both LY 171555 and domperidone were completely ineffective in modulating 5-HT release regardless of the absence or presence of nomifensine.

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Strips of rabbit extrapulmonary, coeliac and mesenteric arteries were mounted in organ baths for isotonic recording of changes in tissue length. The formation by the strips of the vasodilator prostaglandins PGI2 (measured as 6-keto-PGF1 alpha) and PGE2 was determined by specific radioimmunoassays. Removal of vascular endothelium initially increased and then permanently decreased the basal prostaglandin release of the tissues. Acetylcholine (ACh) relaxed strips of all three arteries if the endothelium was intact. ACh also stimulated the formation of PGI2 and PGE2 from all three tissues; about 60% of these prostaglandins originated from endothelial cells. Indomethacin caused complete inhibition of prostaglandins formation and a slight inhibition of the ACh-relaxation (not statistically significant). Complete inhibition of the ACh relaxation was achieved with nordihydroguaiaretic acid (NDGA). NDGA also partially inhibited prostaglandin formation. These data suggest that in blood vessels that are also prostaglandin-sensitive, the ACh relaxation is predominantly mediated by a non-prostaglandin endothelium-derived relaxing factor. Bradykinin was more potent that ACh in releasing prostaglandins from the same arteries. This release was activated in subendothelial components of the vascular wall. Neither this prostaglandin release nor the bradykinin-induced relaxations were significantly reduced in endothelium-denuded arteries. Indomethacin completely blocked the bradykinin-induced prostaglandin release and the bradykinin relaxation. NDGA caused a moderate inhibition of the bradykinin-induced prostaglandin release and slightly attenuated the bradykinin relaxation (neither effect of NDGA was statistically significant). Under all experimental conditions (control, indomethacin, NDGA) and with all three arteries there was a good correlation between the bradykinin-induced prostaglandin release and the respective mechanical response. No such correlation could be found for ACh. Prostaglandin-dependent relaxations of the coeliac and mesenteric artery are probably mediated by endogenous PGI2. The extrapulmonary artery is rather insensitive to PGI2 and is probably relaxed mainly by endogenous PGE2.

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