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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 101-103 
    ISSN: 1432-1912
    Keywords: Prostacyclin (PGI2) ; Cyclic AMP ; Adenosine ; Noradrenaline ; Coronary arteries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of prostacyclin (PGI2) on vascular tension and cAMP content were measured in isolated bovine coronary artery strips. 3 nM PGI2 did not alter the tension but diminished the cAMP content by 56% of the control level (P〈0.005). 30 and 300 nM PGI2 diminished the tension and further reduced the cAMP content, which amounted to only 5% of the control at 300 nM PGI2. These results are in contrast to the increase in cAMP level by PGI2 in blood platelets and might indicate a different mechanism of action of PGI2 in platelets and vascular tissue.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Thromboxane A2 (TXA2) ; Prostacyclin (PGI2) ; Human platelets ; Bovine coronary artery ; Non-steroidal antiinflammatory drugs ; Prostaglandin-cyclooxygenase ; Bioassay ; RCS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and plateletcyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioassayed as RCS on rabbit aorta strips, PGI2 in terms of its antiaggregatory activity on ADP-induced aggregation of human platelet-rich plasma. All of the substances studied produced concentration-dependent inhibition of PGI2- and RCS-release. The IC50 [μM] in inhibition of RCS-formation was 0.019 for indomethacin, 0.070 for tiaprofenic acid but 44.9 for meclofenamate and 63.2 for diclofenac. The IC50 [μM] in inhibition of PGI2-release was 0.42 for diclofenac, 0.63 for indomethacin and 0.99 for tiaprofenic acid. The data suggest (1) high sensitivity of human platelet-cyclooxygenase against indomethacin and tiaprofenic acid, (2) different sequence of the substances studied in inhibiting arachidonic acid-induced TXA2- and PGI2-formation. The possible therapeutic value of selective inhibition of platelets and vascular cyclooxygenases in discussed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 213-217 
    ISSN: 1432-1912
    Keywords: Dihydro-PGI2 ; Prostacyclin (PGI2) ; Bovine coronary artery ; Guinea pig heart ; Myocardial mechanics ; Coronary vascular tone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of the dihydro prostacyclins, (6R)-PGI1 and (6S)-PGI1, was studied on the isolated guinea pig heart and bovine coronary artery strips. PGE2 and PGI2 were used as standards. In the isolated guinea pig heart (6S)-PGI1 decreased the coronary perfusion pressure (CPP), myocardial force of contraction (MFC) and oxygen consumption (QO2). (6R)-PGI1 did not produce a significant change in these parameters. The ED50 (50% of maximum coronary dilation) was approximately 20 times higher for (6S)-PGI1 than for PGI2 or PGE2. Treatment of the hearts with reserpine + tyramine abolished the (6S)-PGI1-induced decrease in MFC but not the decrease in the CPP. The same pattern of responses was seen with PGE2. Bovine coronary artery strips were contracted by both (6S)-PGI1 and (6R)-PGI1, the ED50 (50% of maximum increase in tension) being 5 and 10 times higher than that for PGE2. The (6S)-PGI1-induced contraction was preceeded by a small relaxation, which, however, was much less than that seen after PGI2. It is concluded that the hydration of the 5,6 double bound in the PGI2-like activity and generates PGE-like activity. The same biological activity of both dihydro prostacyclins in the isolated coronary artery strip but not in the intact coronary vascular bed leads to suggest that the sites of action in these systems are different.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 213-221 
    ISSN: 1432-1912
    Keywords: Prostacyclin (PGI2) ; Bradykinin ; Coronary artery ; Guinea pig heart ; Indomethacin ; Oxygen consumption ; Myocardial mechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The action of bradykinin on prostacyclin (PGI2) release and the coronary artery tone was studied in the isolated guinea pig heart and the bovine coronary artery. Myocardial force of concentration and oxygen consumption were monitored continuously. 2. Addition of bradykinin to the guinea pig heart was followed by a dose-dependent decrease in the coronary perfusion pressure, while myocardial contractile force and oxygen consumption remained unchanged, indicating a direct effect on the coronary vascular resistance. There was no evidence for tachyphylaxis. 3. Long-term treatment of the hearts with indomethacin at low concentrations (5×10−7 g/ml) did not influence the bradykinin-induced coronary dilation. Increasing the indomethacin (5×10−6 g/ml) produced a partial (repetitive application) or complete inhibition (cumulative dose-response curves). 4. Application of bradykinin to coronary artery strip also produced relaxation. Indomethacin (2×10−6 g/ml) did only attenuate this effect although it completely prevented the response to arachidonic acid. 5. The release of PGI2-like material from the heart by bradykinin was studied using the cascade-technique of Vane (1969). There was a dose-dependent release of a substance, which relaxed the bovine coronary artery. Pretreatment of the hearts with 15-hydroperoxy arachidonic acid or indomethacin (5×10−6 g/ml) produced a partial or complete inhibition of this response. However, there was no significant inhibition of the bradykinin-induced relaxation of the coronary vascular bed. 6. It is suggested that the inhibitory effect of high dose indomethacin is not due to inhibition of prostaglandin biosynthesis, which is already completely blocked at low doses. According to this, two different actions of indomethacin on the coronary vessels could be established. 7. The results indicate that bradykinin produces a pronounced release of PGI2 from the coronary vessels, which, however, can be blocked without abolition of the coronary relaxing activity. This provides evidence for an additional, PGI2-independent coronary action of this substance.
    Type of Medium: Electronic Resource
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