Aspirin: an Unexpected Side Effect on Prostacyclin Synthesis in Cultured Vascular Smooth Muscle Cells

Whiting, J; Salata, Konrad; Bailey, J. Martyn

doi:10.1126/science.6776627

Cited by 34 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results shown in Table 4 indicate that heparin does not have a n immediate effect on PGI2 production. The time required to induce this inhibitory effect is consistent with that of testosterone (5 days) (Nakao et al, 1981) and is not consistent with that of aspirin (30 min) (Czervionke et al, 1979;Whiting et al, 1980). Furthermore, this inhibitory effect of heparin was not canceled, even if the cells treated with heparin were cultured without heparin.…”

Section: Discussionsupporting

confidence: 54%

Stimulation of cell growth and inhibition of prostacyclin production by heparin in human umbilical vein endothelial cells

Hasegawa

Yamamoto

1988

Journal Cellular Physiology

View full text Add to dashboard Cite

We characterized human umbilical vein (HUV) endothelial cells as to cell growth and prostacyclin production to get a better understanding of the properties of endothelial cells. Endothelial cell growth supplement (ECGS) and basic fibroblast growth factor (FGF) stimulated HUV endothelial cell growth. Heparin further enhanced the cell growth stimulated by ECGS, but not the cell growth stimulated by FGF or in the absence of these growth factors. In the presence of ECGS, the prostacyclin-producing capacity of the cells was inhibited by heparin. However, in the presence of FGF of in the absence of growth factors, heparin did not inhibit prostacyclin production. Therefore, it is likely that there is a specific correlation between heparin and growth factors for endothelial cells in the blood vessel to maintain nonthrombogenicity properly. Heparin-treated cultures may not be suitable for some examinations of prostacyclin production by vascular endothelial cells.

show abstract

Section: Discussionsupporting

confidence: 54%

Stimulation of cell growth and inhibition of prostacyclin production by heparin in human umbilical vein endothelial cells

Hasegawa

Yamamoto

1988

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Complementing these data, Buchanan et al (31) noted that inhibition of prostacyclin biosynthesis by rabbit carotid arteries persisted at least 20 h after exposure to aspirin. Interestingly, although endothelial cells in culture rapidly resynthesize new cyclooxygenase (5), recent data obtained in cultured rat smooth muscle cells suggests that aspirin may destroy additional components of the prostacyclin synthetic system that can only be replaced by cell division (32).…”

Section: Discussionmentioning

confidence: 99%

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

FitzGerald¹,

Oates²,

Hawiger³

et al. 1983

J. Clin. Invest.

642

268

View full text Add to dashboard Cite

A B S T R A C T To assess the pharmacologic effects of aspirin on endogenous prostacyclin and thromboxane biosynthesis, 2,3-dinor-6-keto PGFia (PGI-M) and 2,3-dinor-thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter-and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass spectral identification confirmed continuing prostacyclin biosynthesis during aspirin therapy. Recovery of prostacyclin biosynthesis was incomplete 5 d after drug administration was discontinued. To relate aspirin intake to indices of thromboxane biosynthesis and platelet function, volunteers received 20 mg aspirin daily followed by 2,600 mg aspirin daily, each dose for 7 d in sequential weeks. Increasing aspirin dosage inhibited Tx-M excretion from 70 to 98% of pretreatment control values; platelet TxB2 formation from 4.9 to 0.5% and further inhibited platelet function.An extended study was performed to relate aspirin intake to both thromboxane and prostacyclin genera- tion over a wide range of doses. Aspirin, in the range of 20 to 325 mg/d, resulted in a dose-dependent decline in both Tx-M and PGI-M excretion. At doses of 325-2,600 mg/d Tx-M excretion ranged from 5 to 3% of control values while PGI-M remained at 37-23% of control. 3 d after the last dose of aspirin (2,600 mg/ d) mean Tx-M excretion had returned to 85% of control, whereas mean PGI-M remained at 40% of predosing values. Although the platelet aggregation response (Tmax) to ADP ex vivo was inhibited during administration of the lower doses of aspirin the aggregation response returned to control values during the final two weeks of aspirin administration (1,300 and 2,600 mg aspirin/d) despite continued inhibition of thromboxane biosynthesis.These results suggest that although chronic administration of aspirin results in inhibition of endogenous thromboxane and prostacyclin biosynthesis over a wide dose range, inhibition of thromboxane biosynthesis is more selective at 20 than at 2,600 mg aspirin/d. However, despite this, inhibition of platelet function is not maximal at the lower aspirin dosage. Doses of aspirin in excess of 80 mg/d resulted in substantial inhibition of endogenous prostacyclin biosynthesis. Thus, it is unlikely that any dose of aspirin can maximally inhibit thromboxane generation without also reducing endogenous prostacyclin biosynthesis. These results also indicate that recovery of endogenous prostacyclin biosynthesis is delayed following aspirin administration and that the usual effects of aspirin on platelet function ex vivo may be obscured during chronic aspirin administration in man.

show abstract

“…There is, therefore, some pharmacological basis for reported therapeutic benefits of administering drugs which inhibit PG synthesis in the treatment of vascular headaches, particularly since many agents which precipitate vascular headaches, such as tyramine and alcohol, stimulate prostaglandin biosynthesis. 4 PGI 2 synthesized by the intima of cerebral arterioles, [15][16] is one of the most potent cerebral vasodilators known. [17][18][19][20][21][22][23] It inhibits platelet aggregation, which has been reported to be intermittently enhanced with the headache cycles of migraineurs.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin Inhibition and Cerebrovascular Control in Patients with Headache

Amano

Meyer

1982

Headache

View full text Add to dashboard Cite

SYNOPSISEffects of aspirin and indomethacin on cerebral blood flow (CBF) and cerebral vasomotor responsiveness (VMR) to 5% CO 2 and 100% O 2 inhalation were compared in patients with vascular and non-vascular headaches. Indomethacin was 60 times as potent as aspirin in inhibiting cerebrovascular prostacyclin (PGI 2 ) synthesis in humans, as judged by CBF and VMR effects. 972 mgs of aspirin, a dose known to inhibit thromboxane synthesis and platelet aggregation had minimal effects on CBF (-3.8%), attributed to partial PGI 2 inhibition, since there was no effect on VMR to 5% CO 2 . Indomethacin (25-50 mgs) reduced CBF (-17.8%), VMR to 5% CO 2 (-72%) and VMR to 100% O 2 (-75%). PGI 2 plays an important role in cerebrovascular control of human subjects. Inhibition of PGI 2 synthesis by indomethacin relieves cluster-type headaches more consistently than other headaches. Evidence is offered that 100% O 2 inhalation causes cerebral vasoconstriction by inhibiting cerebrovascular PGI 2 synthesis, thereby benefitting cluster headaches. Migraineurs appear to have excessive PGI 2 synthesis. Patients with hemicephalalgia show asymmetric hemispheric responses to indomethacin, ascribed to asymmetric neurogenic influences on PGI 2 synthesis.

show abstract

Aspirin: an Unexpected Side Effect on Prostacyclin Synthesis in Cultured Vascular Smooth Muscle Cells

Cited by 34 publications

References 11 publications

Stimulation of cell growth and inhibition of prostacyclin production by heparin in human umbilical vein endothelial cells

Stimulation of cell growth and inhibition of prostacyclin production by heparin in human umbilical vein endothelial cells

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

Prostaglandin Inhibition and Cerebrovascular Control in Patients with Headache

Contact Info

Product

Resources

About