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Angiology
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In Vivo and in Vitro Evidence of an Adenosine-Mediated Mechanism of Calcium Entry Blocker Activities

T. Di Perri

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

F. Laghi Pasini

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

S. Pecchi

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

V. De Franco

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

P. Damiani

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

A.L. Pasqui

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

P.L. Capecchi

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

A. Orrico

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

M. Materazzi

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

L. Domini

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

L. Ralli

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

A. Monaci

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

P. Blardi

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

L. Ceccatelli

Istituto di Patologia Speciale Medica e Metodologia Clinica, Universita degli Studi di Siena, Siena, Italy

Drugs such as dipyridamole (200 µg/kg/min), an adenosine uptake in hibitor, and theophylline (300 µg/kg/min), an adenosine receptor antagonist, respectively increased and decreased postischemic hypere mia in normal subjects, as well as in POAD patients. Moreover, dipyrida mole pretreatment was able to antag onize the reduction of peak flow in duced by nifedipine, and the potenti ating effect of flunarizine on postis chemic hyperemia was affected sig nificantly by theophylline, thus sug gesting a possible interference of calcium entry blocker drugs with the endogenous adenosine system. In a cellular model (polymorphonuclear leukocytes — PMN) the inhibitory ef fect of calcium entry blockers on stimulated functions (degranulation and free radical production) was highly antagonized by theophylline. Finally, a 1H-NMR spectroscopy study showed a binding interaction between adenosine and flunarizine on the cell membrane. An adenosine-re ceptor coupling to the calcium entry blocker channels is suggested.

Angiology, Vol. 40, No. 3, 190-198 (1989)
DOI: 10.1177/000331978904000307
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