[Metabolism of several blood prostaglandins in patients with angina pectoris during helium-neon laser therapy]. / Metabolizm nekotorykh prostaglandinov krovi u bol'nykh so stenokardiei na fone gelii-neonovoi lazernoi terapii.

The paper shows the high therapeutical efficiency of combined He-Ne laser therapy in patients with coronary heart disease. Its effect on the thromboxane-prostacyclin system is one of the mechanisms of laser impact. The combined He-Ne laser therapy promotes normalization of the level of thromboxane B2 and its ratio to the metabolite prostacyclin.

[Prostacyclin- and thromboxane synthesis in the vascular wall after gammatron irradiation]. / Prostacyclin- und Thromboxansynthese der Gefässwand nach Gammatronbestrahlung.

One year aged rabbits were exposed to a single dose of 100, 500 or 1000 rd (1.0, 5.0 or 10 Gy) to the abdominal aorta. The non-irradiated thoracic aortic segment served as control. The animals were killed between one and 336 hours after the irradiation. Four animals were examined in each group. The prostacyclin formation was assessed by means of a radioimmunoassay against its stable breakdown 6-oxo-PGF1 alpha, the thromboxane A2-formation using a radioimmunoassay for thromboxane B2. Local irradiation causes a temporary increase of both the compounds. In contrast to thromboxane B2, the 6-oxo-PGF1 alpha exhibits a long-lasting depression. The higher the radiation dose, the more intensive the increase and the long-lasting depression of 6-oxo-PGF1 alpha. The liberation of eicosanoids and subsequent hemostatic dysregulation at different intervals after irradiation might contribute to an important extent to the radiation induced vasculopathy.

Irradiation depresses prostacyclin generation upon stimulation with the platelet-derived growth factor.

Experimental and clinical findings demonstrated rather severe arterial lesions occurring in irradiated arteries. It is suggested that a local haemostatic imbalance might be one causative factor. Liberation of PDGF causes smooth-muscle cell proliferation and PGI2 formation by the arterial wall cells, inhibiting in turn further release of PDGF from the alpha granules of the platelets. A decreased ability of irradiated vascular segments to generate PGI2 upon PDGF stimulation described here might cause haemostatic imbalance and subsequent radiation-induced lesions.

Identification of the prostacyclin receptor by radiation inactivation.

Evidence has been obtained for a specific protein receptor for prostacyclin on cells of the NCB-20 somatic hybrid. A new stable prostacyclin analog, 5-[(E)-(1S,5S,6R,7R) - 7 - hydroxy-6-[(E) - (3S,4RS) -3-hydroxy-4-methyl-1 -octen-6-inyl]bicyclo[3.3.0]-octan-3-ylidene]pentanoic acid (Iloprost, ZK36374) activates adenylate cyclase of NCB-20 cell membranes to an extent similar to prostacyclin and with a comparable high affinity. The binding of [3H]Iloprost to NCB-20 membranes was rapid with an association rate constant (k+1) of 2.01 X 10(5) M-1 s-1 at 20 degrees C. The rate constant for the dissociation of the ligand-receptor complex (k-1) was 1.19 X 10(-3) s-1, giving a dissociation constant (k-1/k+1) of 5.9 nM. The equilibrium dissociation constant was 29.9 nM, and the membranes had a maximum binding capacity of 347 fmol mg-1 protein. Radiation inactivation has been employed to determine the molecular weights of the functional prostacyclin receptor and components of the adenylate cyclase system in the plasma membrane of the NCB-20 cells. Cell membranes were lyophilized prior to irradiation, which lead to the formation of high-molecular-weight aggregates. The aggregation was avoided, however, when membranes were prepared in an isotonic Tris-HCl buffer containing sucrose. Molecular weight values of 111,000 for the catalytic subunit of adenylate cyclase, 89,000 for the regulatory subunit, and 83,000 for the prostacyclin receptor were obtained. Loss of [3H]Iloprost binding capacity after irradiation of lyophilized membranes yielded a molecular weight value (mean +/- S.E.) for the prostacyclin receptor of 82,800 +/- 12,900 (n = 3).

Radiation injury in rat lung. I. Prostacyclin (PGI2) production, arterial perfusion, and ultrastructure.

Pulmonary prostacyclin (PGI2) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI2 production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P less than 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI2 as did either shielded left lung or sham-irradiated lungs (P less than 0.05). Perfusion scans revealed hyperemia of the right lung from 1 to 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI2 production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI2. Pulmonary PGI2 production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.

[Effect of 60Co gamma rays and fast neutrons on intravascular platelet aggregation and vessel wall prostacyclin activity]. / Vliianaie gamma-luchei 60Co i bystrykh neitronov na vnutrisosudistuiu agregatsiiu trombotsitov i prostatsiklinovuiu aktivnost' stenki sosudov.

The influence of gamma-rays 60Co and fast neutrons on intravascular platelet aggregation and prostacyclin activity of the vascular wall has been studied. It has been shown that 1-6 hours after irradiation of CBA mice, a great number of bone marrow platelets clump to form fibrin fibrils that often close completely the vascular lumen. Experiments with irradiated rats and guinea-pigs have demonstrated the reduction of prostacyclin-like activity in the abdominal aorta wall.