Streptozocin-induced diabetes decreases formation of prostacyclin from arachidonic acid in intact rat lungs

William C. Lubawy; Monica Valentovic

doi:10.1016/0006-2944(82)90082-5

Streptozocin-induced diabetes decreases formation of prostacyclin from arachidonic acid in intact rat lungs

William C. Lubawy, Monica Valentovic

Pharmaceutical Sciences

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Abstract

Diminished vascular prostacyclin (PGI₂), as well as elevated platelet thromboxane (TXA₂) generation is known to occur in diabetes and may be involved in the thrombotic and atherosclerotic complications of this disease. Pulmonary tissue synthesizes both PGI₂ and TXA₂; however, alterations in the generation of these substances in diabetic lungs has not been reported. We determined PGI₂ and TXA₂ generation from ¹⁴C arachidonic acid in isolated perfused lungs obtained from male rats 1 and 14 days after a 50 mg/kg i.v. dose of streptozocin or the citrate-buffer vehicle. Compared to controls, lungs from rats made diabetic for 14 days showed a 30% decrease in PGI₂ generation with no change in TXA₂. A direct inverse relationship of pulmonary PGI₂ TXA₂ ratios to plasma glucose levels for the 14-day diabetic rats occurred (r² = -0.886). The 1-day study showed no difference between control and diabetic rats which suggests that alterations in arachidonic acid metabolism observed after 14 days are the result of the diabetic condition and not streptozocin. These data indicate that pulmonary PGI₂ synthesis is altered by diabetes of short duration in a manner similar to vascular tissue.

Original language	English
Pages (from-to)	290-297
Number of pages	8
Journal	Biochemical medicine
Volume	28
Issue number	3
DOIs	https://doi.org/10.1016/0006-2944(82)90082-5
State	Published - Dec 1982

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title = "Streptozocin-induced diabetes decreases formation of prostacyclin from arachidonic acid in intact rat lungs",

abstract = "Diminished vascular prostacyclin (PGI2), as well as elevated platelet thromboxane (TXA2) generation is known to occur in diabetes and may be involved in the thrombotic and atherosclerotic complications of this disease. Pulmonary tissue synthesizes both PGI2 and TXA2; however, alterations in the generation of these substances in diabetic lungs has not been reported. We determined PGI2 and TXA2 generation from 14C arachidonic acid in isolated perfused lungs obtained from male rats 1 and 14 days after a 50 mg/kg i.v. dose of streptozocin or the citrate-buffer vehicle. Compared to controls, lungs from rats made diabetic for 14 days showed a 30% decrease in PGI2 generation with no change in TXA2. A direct inverse relationship of pulmonary PGI2 TXA2 ratios to plasma glucose levels for the 14-day diabetic rats occurred (r2 = -0.886). The 1-day study showed no difference between control and diabetic rats which suggests that alterations in arachidonic acid metabolism observed after 14 days are the result of the diabetic condition and not streptozocin. These data indicate that pulmonary PGI2 synthesis is altered by diabetes of short duration in a manner similar to vascular tissue.",

author = "Lubawy, {William C.} and Monica Valentovic",

note = "Funding Information: This work was supported in part by University of Kentucky Tobacco and Health Research Institute Project 4FOO6. The authors wish to thank Ms. Brenda Culpepper for technical assistance and Dr. James Munson, the Upjohn Company, for generously supplying prostaglandin standards.",

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AU - Valentovic, Monica

N1 - Funding Information: This work was supported in part by University of Kentucky Tobacco and Health Research Institute Project 4FOO6. The authors wish to thank Ms. Brenda Culpepper for technical assistance and Dr. James Munson, the Upjohn Company, for generously supplying prostaglandin standards.

PY - 1982/12

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N2 - Diminished vascular prostacyclin (PGI2), as well as elevated platelet thromboxane (TXA2) generation is known to occur in diabetes and may be involved in the thrombotic and atherosclerotic complications of this disease. Pulmonary tissue synthesizes both PGI2 and TXA2; however, alterations in the generation of these substances in diabetic lungs has not been reported. We determined PGI2 and TXA2 generation from 14C arachidonic acid in isolated perfused lungs obtained from male rats 1 and 14 days after a 50 mg/kg i.v. dose of streptozocin or the citrate-buffer vehicle. Compared to controls, lungs from rats made diabetic for 14 days showed a 30% decrease in PGI2 generation with no change in TXA2. A direct inverse relationship of pulmonary PGI2 TXA2 ratios to plasma glucose levels for the 14-day diabetic rats occurred (r2 = -0.886). The 1-day study showed no difference between control and diabetic rats which suggests that alterations in arachidonic acid metabolism observed after 14 days are the result of the diabetic condition and not streptozocin. These data indicate that pulmonary PGI2 synthesis is altered by diabetes of short duration in a manner similar to vascular tissue.

AB - Diminished vascular prostacyclin (PGI2), as well as elevated platelet thromboxane (TXA2) generation is known to occur in diabetes and may be involved in the thrombotic and atherosclerotic complications of this disease. Pulmonary tissue synthesizes both PGI2 and TXA2; however, alterations in the generation of these substances in diabetic lungs has not been reported. We determined PGI2 and TXA2 generation from 14C arachidonic acid in isolated perfused lungs obtained from male rats 1 and 14 days after a 50 mg/kg i.v. dose of streptozocin or the citrate-buffer vehicle. Compared to controls, lungs from rats made diabetic for 14 days showed a 30% decrease in PGI2 generation with no change in TXA2. A direct inverse relationship of pulmonary PGI2 TXA2 ratios to plasma glucose levels for the 14-day diabetic rats occurred (r2 = -0.886). The 1-day study showed no difference between control and diabetic rats which suggests that alterations in arachidonic acid metabolism observed after 14 days are the result of the diabetic condition and not streptozocin. These data indicate that pulmonary PGI2 synthesis is altered by diabetes of short duration in a manner similar to vascular tissue.

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Streptozocin-induced diabetes decreases formation of prostacyclin from arachidonic acid in intact rat lungs

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