Lungs as a generator of prostacyclin — Hypothesis on physiological significance

Gryglewski, R; Korbut, R; Ocetkiewicz, A.; Spławiński, Jacek; Wojtaszek, B.; Święes, J.

doi:10.1007/bf00501376

Cited by 81 publications

(18 citation statements)

References 26 publications

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“…The present results are in agreement with in vitro studies with the aggregometer in whch PGI2 was a potent inhibitor of platelet aggregation Gryglewski et al, 1976;Lefer et aL, 1978). It has been reported recently that isolated perfused lungs of rats and guinea pigs and the lungs of anesthetized cats spontaneously release a "PGI2-like" substance (Gryglewski et aL, 1978). If the lungs release "PGl2-like" substances and these factors are formed by endothelial cells in upstream vessels, it is possible that these substances serve to inhibit platelet aggregation and thrombus formation in the lung and to maintain the pulmonary vascular bed in a dilated state.…”

Section: Discussionsupporting

confidence: 92%

“…Prostacyclin decreases systemic arterial pressure in all species in which it has been studied, and a PGI 2 analog has been shown to have marked vasodilator activity in the feline pulmonary lobar and mesenteric vascular beds Paustian et al, 1977;Armstrong et al, 1978;Fitzpatrick et al, 1978;Lefer et al, 1978). Although PGI 2 is formed in blood vessels, "PGl2-like" substances are released from the lung, and the metabolite, 6-keto-PGFi a , is released from the lung after immunological challenge, the direct effects of PGI 2 on the pulmonary vascular bed are uncertain (Dawson et al, 1976;Gryglewski et aL, 1976;Gryglewski et al, 1978). In a recent study in the anesthetized dog, PGI 2 , in a dose of 0.5 fig/kg, iv, caused a 1.4% decrease in pulmonary arterial pressure (Fitzpatrick et al, 1978).…”

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confidence: 99%

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Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Hyman¹,

Kadowitz²

1979

Circulation Research

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IN the lung, arachidonic acid is transformed into the cyclic endoperoxide intermediates, PGG2 and PGH 2 , by a microsomal cyclooxygenase (Nugteren and Hazelhof, 1973;Hamberg and Samuelsson, 1974). The endoperoxide intermediates then are converted by specific terminal enzymes into prostaglandins (PG), thromboxane A2, and a newly discovered bicyclic prostaglandin, prostacyclin, or PGI 2 (Nugteren and Hazelhof, 1973;Hamberg and Samuelsson, 1974;Gryglewski et al., 1976). PGI 2 is the major metabolic product formed from arachidonic acid and endoperoxide intermediates in vascular tissue and, since PGI 2 is a potent inhibitor of platelet aggregation, it has been postulated that it may serve to protect vessel endothelium from the adverse effects of intravascular platelet aggregationFrom the

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Hyman¹,

Kadowitz²

1979

Circulation Research

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“…We have, therefore, suggested that under resting conditions, the pulmonary vascular bed is maintained in a dilated state by production of a vasodilator product in the cyclooxygenase pathway (28). Recent evidence suggests that this vasodilator product in the cyclooxygenase pathway is a PGI2-like substance (6,23,24). It would therefore be of interest to ascertain if industrial pollutants such as NO2 or S02 have adverse effects on enzymes such as cyclooxygenase or prostacyclin synthetase which function to synthesize PGI2 which serves to maintain the pulmonary vascular bed in a dilated state under resting conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The endoperoxide intermediates (PGG2 and PGH2) are then converted by terminal enzymes into primary prostaglandins (PG), thromboxane A2 (TXA2) or prostacyclin, PG12 (2)(3)(4)(5)(6)(7)(8)(9). The distribution and activity of terminal enzymes determine the pattern of products formed from endoperoxide intermediates in an organ (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins Evoke a Whole Variety of Responses in the Lung

Kadowitz¹,

Spannhake²,

Hyman³

1980

Environmental Health Perspectives

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Rapid intravenous (IV) injections of the prostaglandin precursor arachidonic acid (AA) increase pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in a variety of species. It has recently been reported that infusions of AA decrease PAP. The purpose of this report is to contrast responses to bolus injections and infusions of AA in the anesthetized cat. In all experiments rapid IV injections of AA increased PAP and PVR; however, infusions of 68 to 680 ,ug/min produced variable responses. In 10 of 19 animals, AA infusion decreased PAP and PVR, and this response was enhanced when pulmonary vascular tone was actively increased by vasoconstrictor agents or alveolar hypoxia. In the other nine animals, the predominant response was an increase in PAP and PVR. In all experiments infusions of larger amounts of AA (1.4 to 3.4 mg/min) increased PAP. Both pressor and depressor responses to AA were inhibited by meclofenamate. This study shows that infusion of small amounts of AA dilates or constricts the pulmonary vascular bed. In contrast, infusion of larger amounts of AA always causes vasoconstriction.These data suggest that at low infusion rates, PGI2, which is a vasodilator, is the predominant metabolite formed from AA in some animals. However, at higher concentrations, the production of constrictor products predominates. These experiments also suggest that the products formed and the response observed may be dependent on a number of factors including the amount of tone present in the pulmonary vascular bed.

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“…Hyperventilation is known to lead to the release of prostacyclin from the lungs (16)(17)(18). PGI2, in turn, is a potent pulmonary vasodilator of fetal and newborn lung (6, 7, 9).…”

Section: Control Tcpmentioning

confidence: 99%

Effects of Hyperventilation on Prostacyclin Formation and on Pulmonary Vasodilation after Group B β-Hemolytic Streptococci-Induced Pulmonary Hypertension

Hammerman

Aramburo

1991

Pediatr Res

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ABSTRACT. Prostacyclin is released during hyperventilation (HV); however, its role as mediator of HV-induced pulmonary vasodilation remains controversial. We have investigated this by studying the effects of HV on pulmonary artery pressure (PAP) in otherwise normal lungs versus lungs vasoconstricted with group B streptococci (GBS), with and without prior prostacyclin synthesis inhibition. Two-to 3-wk-old piglets were given tranylcypromine, a prostacyclin synthetase inhibitor (n = 6), or placebo (n = 6). Animals were mechanically ventilated normally, then hyperventilated (Pco2 1.5 * 0.2 kPa) and then returned to normal ventilation. After each 30-min segment, plasma 6-keto-prostaglandin F1, (6-keto-PGF,,) (prostacyclin hydrolysis product) levels and PAP were measured. Then GBS infusions were administered to both groups to induce pulmonary hypertension. With GBS, the normal ventilation/hyperventilation/normal ventilation protocol was repeated as above. Results are as follows: I) HV of normal lungs caused release of 6-keto-PGF,, (351 f 234 to 873 + 310 pg/mL; p e 0.05), but PAP was unaffected (1.4 f 0.2 kPa); 2) HV of lungs vasoconstricted with GBS caused a similar release of 6-keto-PGF,, (595 f 112 to 977 + 216 pg/mL; p < 0.05), this time accompanied by a significant decrease in PAP (3.1 2 0.5 to 2.3 f 0.5 kPa; p < 0.05); 3) HV of normal lungs pretreated with tranylcypromine produced neither an increase in 6-keto-PGF,, (400 + 24 to 436 f 33 pg/mL) nor a decrease in PAP (1.3 f 0.2 to 1.4 f 0.2 kPa; and 4) HV after tranylcypromine pretreatment and GBS-induced pulmonary hypertension also produced no change (6-keto-PGF,,: 527 + 54 to 556 f 93 pg/mL and PAP; 39.5 f 6.2 to 37.6 2 6.7 kPa). In conclusion, prostacyclin may mediate HV-induced pulmonary vasodilation after GBS-induced pulmonary hypertension. (Pediatr Res 29: 282-287,1991) Abbreviations PAP, pulmonary artery pressure GBS, group B &hemolytic streptococci PGF,,, prostaglandin F,, Tcp, tranylcypromine ' PVR, pulmonary vascular resistance AOP, aortic pressure HR, heart rate SVI, stroke volume index TxB2, thromboxane B2 Hyperventilation is able to alleviate the pulmonary vasoconstriction induced by hypoxia (1) and/or by the infusion of the thromboxane mimetic, U46 6 19 (2). Clinically, hyperventilation alkalosis has become a central component of the treatment of persistent pulmonary hypertension of the newborn (3), a syndrome characterized by persistent and excessive pulmonary vasoconstriction.However, the mechanism by which hyperventilation induces pulmonary vasodilation remains controversial. Prostacyclin is a potent pulmonary vasodilator that is released during hyperventilation and has been proposed by some to play a mediating role (4-8). In this study, we examined the effects of hyperventilation on 6-keto-PGF,, concentrations and on pulmonary artery pressure and on their interaction under various conditions. Our goals were to test the following hypotheses: 1 ) effects of hyperventilation on 6-keto-PGF,, concentrations and on pulmonary artery pressure in othe...

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Lungs as a generator of prostacyclin — Hypothesis on physiological significance

Cited by 81 publications

References 26 publications

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Prostaglandins Evoke a Whole Variety of Responses in the Lung

Effects of Hyperventilation on Prostacyclin Formation and on Pulmonary Vasodilation after Group B β-Hemolytic Streptococci-Induced Pulmonary Hypertension

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