Effects of the oestrous cycle on the metabolism of arachidonic acid in rat isolated lung.

Abstract

SUMMARY1. The metabolism of exogenous arachidonic acid perfused through the pulmonary circulation was investigated in lungs taken from rats at different stages ofthe oestrous cycle.2. Following perfusion with [14C]arachidonic acid there was more radioactivity associated with cyclo-oxygenase products in general at pro-oestrus than at any other stage of the cycle.3. Production of6-oxo-prostaglandin Fa, and hence ofprostacyclin (PGI2) was also highest at pro-oestrus.4. Production of thromboxane B2 was highest at pro-oestrus although it was never greater than PGI2 production at any stage.5. Radioactivity retained in lung tissue was mostly present in phospholipid and free fatty acid fractions with the distribution at pro-oestrus being different from the other stages.6. Following perfusion with [14C]oleic acid (which is not a substrate for cyclooxygenase), variations in the distribution of label in radioactivity in lung were also observed. However, these were not related to the stages of the oestrous cycle in the same way as those associated with arachidonic acid.7. We conclude that both pathways of arachidonic acid metabolism in lungoxidation via cyclo-oxygenase and incorporation into phospholipid -are affected by the progress of the oestrous cycle.8. Altered arachidonate metabolism appeared to be associated chiefly with prooestrus and may be linked to those hormones involved in this stage of the oestrous cycle.

Metabolism and uptake of adenosine in rat isolated lung and its inhibition

“…Because adenosine is anti-aggregatory (Born & Cross, 1963;Dodds, 1978), its removal from the vascular space into cells could have important consequences for platelet-vessel wall interactions and thrombosis. We have therefore undertaken a study of the fate of adenosine in isolated lungs from rats, a model in which we have already studied other metabolic reactions and uptake mechanisms of relevance to platelet behaviour (Alabaster & Bakhle, 1970;Al-Ubaidi & Bakhle, 1980;Bakhle, Lewis & Watts, 1982;Watts, Zakrzewski & Bakhle, 1982).…”

Estrogen potentiates constrictor prostanoid function in female rat aorta by upregulation of cyclooxygenase-2 and thromboxane pathway expression

“…For example, estrogen treatment enhances PGI 2 production in intact rat aorta (43) and in cultured rat aortic VSM (13) and ovine fetal pulmonary arterial endothelial cells (70). In the isolated, perfused rat lung, AA-induced production of PGI 2 and TxA 2 , which reflects COX activity, varies during the course of the estrous cycle and peaks during the estrogen surge at proestrus (3). Similarly, the pretreatment of isolated, blood-perfused lungs of juvenile female sheep with estradiol enhances the production of TxA 2 (76).…”

The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

“…Previous work had shown an effect of the oestrous cycle on the metabolism of 5-hydroxytryptamine (5-HT) and arachidonic acid in the lungs from female rats (Bakhle & Ben-Harari, 1979a;Bakhle & Zakrzewski, 1982). Since the major nucleotidase activity in rat lung was an ADPase, we measured ADP hydrolysis in lungs taken from female rats at different stages of the oestrous cycle.…”

“…In A, the substrate was given as a bolus injection of 10 nmole and effluent collected for 15 s. In human lung (B) the substrate was infused for 10 s to give a final concentration of 10 /tM and effluent collected for the first minute. ADP hydrolysis in female rat lungs Previous work had shown an effect of the oestrous cycle on the metabolism of 5-hydroxytryptamine (5-HT) and arachidonic acid in the lungs from female rats (Bakhle & Ben-Harari, 1979a;Bakhle & Zakrzewski, 1982). Since the major nucleotidase activity in rat lung was an ADPase, we measured ADP hydrolysis in lungs taken from female rats at different stages of the oestrous cycle.…”

“…Human lung samples were obtained from patients of either sex. Female Wistar rats (200-250 g) were housed under controlled lighting conditions and their oestrous cycle checked by vaginal smears (Bakhle & Zakrzewski, 1982). We thank Mr J. T. Zakrzewski for the monitoring of the oestrous cycle of the female rats used in these experiments.…”