S U M M A R Y The responses of baboon cerebral and extracerebral arteries to prostaglandin endoperoxide (PGH2) and prostacyclin (PGI2) were investigated on isolated arteries and in vivo by serial angiography. Both PGH2 and PGI2 could produce dose-dependent contraction or relaxation of isolated arteries. PGH2 induced relaxation was indicative of prostacyclin synthetase activity, the enzyme which converts PGH2 to PGI2. In isolated arteries tested one to four hours post mortem only the vertebral artery showed prostacyclin synthetase activity. Thus PGH2 induced contraction of cerebral arteries may be indicative of a physiological function. Vasomotor tone may in part be the result of a balance between PGH2 constriction and PGI2 dilatation. In vivo PGI2 infusion caused pronounced and prolonged dilatation of cerebral arteries, which lasted longer than the cardiovascular changes. As PGI2 is the most potent cerebral vasodilator drug tested, it may be of clinical use in the treatment of cerebral vasospasm.Prostacyclin is a recently discovered prostaglandin with potent vasodilator effects on peripheral and central blood vessels. In addition prostacyclin is one of the most potent inhibitors of platelet aggregation known. The potential therapeutic applications of the use of this drug or more stable analogues is currently under study (Moncada and Vane, 1978).In view of its potent relaxing actions on human and baboon cerebral arteries (Boullin et al., 1979) prostacyclin may be of use in the prevention or reversal of cerebral arterial vasospasm which commonly occurs after the rupture of aneurysms of the major cerebral arteries.Before any clinical studies it is of course necessary to examine the actions of prostacyclin and precursors (prostaglandin endoperoxides, PGG2, PGH2) upon the cerebral vasculature of animals.For some years we have been using the baboon as a model for studying the aetiology of human vasospasm (see Boullin et al., 1977.
The a-and 3-adrenoceptor activities of the isolated rat uterus during the oestrous cycle were intluenced greatly by temperature changes. During dioestrus, lowering the bath temperature to 250C from 400C increased two-fold the inhibition produced by (-)-adrenaline, (-)-noradrenaline, (-)-phenylephrine and (-)-isoprenaline. During oestrus adrenaline, noradrenaline and phenylephrine produced biphasic responses of contraction followed by inhibition at 40°C and isoprenaline produced only inhibition. At 250C the contractile a-responses either were abolished (phenylephrine) or greatly reduced (adrenaline and noradrenaline), while the inhibitory ,-effects of all four amines were increased.It has been generally accepted since the time of Ahlquist ( 1948) that the uterus of the rat contains f-adrenoceptors. However, Mann (1949) found that the uterus of the rat in oestrus contracted to noradrenaline and that there was a biphasic response to adrenaline. Butterworth & Randall (1970) showed that these effects are due to the presence of both at-and ,B-adrenoceptors throughout the oestrous cycle. Some workers (e.g. Rudzik & Miller, 1962;Levy & Tozzi, 1963;Tothill, 1967) have disputed the presence of excitatory ca-adrenoceptors within the normal oestrous cycle. There is now evidence that endogenous prostaglandins may be involved in motor responses of the uterus (Tothill, Rathbone & Willman, 1971;Aiken, 1972;Vane & Williams, 1973). This paper describes a study of the effect of temperature on the relative a-and B-adrenoceptor activities throughout the oestrous cycle.Methods Virgin, albino rats (Wistar strain), weighing 200-250 g, were used. The sexual state of the rat was determined by taking a vaginal smear immediately before killing by a blow to the head and bleeding out. The uterine horns were excised and 2-3 cm of the tissue from the ovarian end were set up in a 15 ml organ bath containing Tyrode solution aerated with 5% CO2 in 02. Uterine movements were recorded with an isotonic frontal writing lever (weight 0.5 g), moving on a smoked drum. Rats were used either in dioestrus or in oestrus, which was either natural or induced by oestradiol benzoate (0.5 mg s.c. given 3 days beforehand). After setting up the preparations, at least I h was allowed for the tissues to equilibrate before starting the experiment. The recordings were made at 400, 30°and 250 C. Thirty minutes were allowed to ensure that the uterus had settled down each time the bath temperature was altered. Doses were determined for each sympathomimetic amine which gave approximately 90% of a maximal contraction, or 50% inhibition of a near maximal response to acetylcholine. ResultsRats in dioestrus At the temperatures studied, all four amines produced solely inhibitory responses. At 40 C the mean inhibitory doses were phenylephrine (Phe) 12 ,g (range, 5 to 20 Mg, n = 5), noradrenaline (NA) 1.5 gg (0.75 to 2 ,g, n = 6), adrenaline (Ad) 18 ng (7 to 45 ng, n = 6) and isoprenaline (Iso) 4 ng (2 to 6 ng, n = 5). As the temperature was lowered, first to 30 C and then to 25...
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