Airway and vascular effects of 8-epi-prostaglandin F2 alpha in isolated perfused rat lung

Abstract

The effects of 8-epi-prostaglandin (PG) F2 alpha, a recently discovered noncyclooxygenase free radical-catalyzed product of arachidonic acid, on pulmonary vascular and airway tone, its potency, and its mechanism of action were studied. Progressively increasing bolus doses (1.0, 5.0, 10.0, and 20.0 micrograms) of 8-epi-PGF2 alpha were injected into the pulmonary artery catheter of 18 isolated rat lungs, and a single dose (40.0 micrograms) was injected into 7 additional rat lungs. The lungs were perfused with Krebs-Henseleit buffer solution containing 3% bovine serum albumin at 50 ml.kg-1.min-1 during ventilation with 21% O2-5% CO2-74% N2. 8-Epi-PGF2 alpha caused rapid pulmonary vascular and airway constrictor responses, which were followed by a gradual return over 10 min to baseline levels. Double vascular occlusion at peak rise in pulmonary arterial pressure (Ppa) revealed a 28% increase in arterial resistance. The rise in Ppa with 20 micrograms of 8-epi-PGF2 alpha was approximately twofold greater than with 20 micrograms of the cyclooxygenase-derived prostaglandin PGF2 alpha. The addition of 100 microM N-nitro-L-arginine, a blocker of endothelium-derived relaxing factor, in the perfusate potentiated the rise in Ppa by 244%. Injection of 40 micrograms of rat atrial natriuretic factor at peak response to 20 micrograms of 8-epi-PGF2 alpha accelerated the return to baseline Ppa, resistance to airflow across the lung, and dynamic lung compliance values.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased isoprostane levels in oleic acid-induced lung injury

“…It has been reported that isoprostane is a modest pulmonary vasoconstrictor [10][11][12] and the levels in urine were increased in patients with pulmonary hypertension [9]. In the present study, mild pulmonary hypertension persisted after oleic acid administration [14].…”

“…On the other hand, 8-epi-PGF2α was reported to cause bronchoconstriction, although species differences were observed [10,26]. No information was available about the effects of isoprostane on bronchial smooth muscle in sheep.…”

“…In addition, the increases are inversely correlated with pulmonary vasoreactivity as measured by decreased pulmonary vascular resistance in response to inhaled nitric oxide. Indeed, isoprostane has been shown to be a modest pulmonary vasoconstrictor [10][11][12].…”

Augmented Vasoconstriction and Thromboxane Formation by 15-F 2t -Isoprostane (8-Iso-Prostaglandin F 2α ) in Immature Pig Periventricular Brain Microvessels

“…[13][14][15][16][17][18][19] 15-F 2t -Isoprostane (15-F 2t -IsoP) (8-iso-prostaglandin F 2␣ ) 20 is one of the abundantly generated isoprostanes in vivo; it is a potent renal, coronary, pulmonary, retinal, and cerebral vasoconstrictor. 7,18,[21][22][23][24] Although the vasomotor effects of 15-F 2t -IsoP are largely inhibited by TXA 2 receptor blockers, 7,[22][23][24] 15-F 2t -IsoP does not seem to bind directly with the TXA 2 receptor. [25][26][27] We recently reported that 15-F 2t -IsoP causes marked constriction of retinal vessels of piglets by stimulating TXA 2 synthesis, 21 but such cyclooxygenase-dependent action of this isoprostane has not been uniformly observed in other vascular beds.…”

Oxidative stress may explain how hypertension is maintained by normal levels of angiotensin II

“…Chronic treatment (9 months) with the antioxidant vitamin E normalizes renal isoprostane levels and improves glomerular filtration rate significantly (47). In rabbits and rats, isoprostane is also a potent pulmonary artery vasoconstrictor and causes bronchoconstriction in the rat lung (48,49). In addition, isoprostane has been shown to induce a significant release of ET from bovine aortic endothelial cells (23).…”