Cyclic phosphodiesterase activity and the action of papaverine

The effects of some phosphodiesterase inhibitors on the conductance of the perfused vascular beds of the chloralosed cat

“…The relaxation and contraction process of vascular smooth muscle has not been fully elucidated (Somlyo & Somlyo, 1968;Mellander & Johansson, 1968) but it is probable that cyclic AMP is involved (Triner et al, 1970;Volicier & Hynie, 1971). As suggested by the activities found in this study, the phosphodiesterase in different arteries may vary and hence drugs acting in this manner may be more effective in some vascular beds than in others.…”

“…In the splanchnic bed, the active phosphodiesterase inhibitors produced dose-dependent increases in vascular conductance; papaverine was approximately twelve times more active than theophylline and eight times more active than dipyridamole. Kukovetz & Poch (1970) reported that phosphodiesterase extracted from beef coronary arteries was twenty-five times more sensitive to inhibition by papaverine than by theophylline, and three times more sensitive to papaverine than to dipyridamole, whereas Triner et at. (1970) found papaverine to be fifteen times more active than theophylline in inhibiting the enzyme obtained from rat aorta.…”

“…The studies of Bartelstone & Nasmyth (1963), and of Bartelstone, Nasmyth & Telford (1967), indicated that vasoconstrictors increased the level of cyclic AMP although Robison & Sutherland (1970) claimed the converse to be the case, and Triner, Vulliemoz, Schwartz & Nahas (1970) and Volicier & Hynie (1971) showed that vasodilatation was associated with an accumulation of cyclic AMP.…”

Effects of Dipyridamole on Neurogenic and Non‐neurogenic Dilator Responses of Arterial Smooth Muscle

“…Rather it appears that dipyridamole is potentiating muscular relaxation at a post-synaptic level, probably by increasing intracellular cyclic AMP levels (Triner, Vulliemoz, Schwartz & Nahas, 1970;Robison, Butcher & Sutherland, 1971). This could occur through inhibition of phosphodiesterase (Senft, 1968;Triner, et al, 1970;Vigdahl et al, 1971;Triner, Vulliemoz, Verosky, Habif & Nahas, 1972), although the ability of various drugs to potentiate inhibitory responses of smooth muscle to adenine compounds does not appear to correlate well with their potency as phosphodiesterase inhibitors (Satchell et al, 1972;Hamilton, 1972). An alternative mechanism of action would be by alteration of the metabolism or sequestration of muscle cell adenosine.…”

The Effect of a Xanthine Derivative, 1‐(5′oxohexyl)‐3‐methyl‐7‐propylxanthine (Hwa 285), on Heart Performance and Regional Blood Flow in Dogs and Rabbits

“…theophylline (1,3-dimethyl-xanthine) or any other xanthine derivative with a substituent in 1-position blocks the action of adenosine, probably by competing for its receptors (Scholtholt, Nitz & Schraven, 1972) and produces slight bradycardia (Sakurai & Komarek, 1974), whereas pentoxifilline [(3,7-dimethyl-1-(5-oxohexyl)-xanthine] blocks phosphodiesterase activity (Stefanovich, 1973) and thus increases the content of cyclic adenosine 3',5'-0007-1188/81/040723-008 $01 .00 * monophosphate (cyclic AMP) (Triner, Vulliemoz, Schwartz & Nahas, 1970) with a positive chronotropic and inotropic effect on the heart (Sakurai & Komarek, 1974) and a dilator effect in different vessels in the periphery (Popendiker et al, 1971). Exchange of the methyl group of pentoxifilline in position 7 for a propyl residue increases its solubility in lipids and is supposed to improve its transport across the capillary wall and into the cells.…”