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Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo.
Authors:C J Benoy   M S El-Fellah   R Schneider     O L Wade
Abstract:1. The inactivation of prostaglandin E2 by the rabbit lung was estimated in vivo by comparing its depressor potency following intravenous and intra-aortic injections, and in vitro by measuring the rate of disappearance of smooth muscle stimulating activity when the prostaglandin was incubated with high speed supernatant fractions from lung homogenates. 2. The ability of the lung to inactivate prostaglandin E2 in vivo increased gradually throughout pregnancy, and then decreased rapidly during the three days post-partum. 3. An increased lung inactivation was also seen in pseudopregnant (day 12) rabbits, and in non-pregnant rabbits treated with progesterone for 12 days. A further increase occurred when progesterone treatment was prolonged to 26 days. 4. Treatment with oestradiol monobenzoate or cortisol for 12 days, and deprivation of ovarian hormones for 14-17 days by ovariectomy, were without effect on the lung inactivation of prostaglandin E2. 5. The in vitro experiments revealed a striking increased in the activity of lung prostaglandin metabolizing enzymes during pregnancy. 6. The results are discussed in relation to the hormonal changes occurring during pregnancy, and it is suggested than an enhanced lung inactivation of prostaglandins might have an important protective function at this time.
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