Studies on the mechanism of action of various vasodilators.

1 The vascular relaxant effects of histamine, adenosine, isoprenaline nitroglycerine, papaverine and 3-isobutyl-l-methylxanthine (IBMX) were assessed individually, in strips of rabbit renal artery moderately contracted with noradrenaline (NA) in the absence or presence of phosphodiesterase inhibitors (papaverine and IBMX) or verapamil, a Ca(2+) antagonist.2 The vasodilator effect of histamine was potentiated by papaverine (6.1 x 10(-7) M) and IBMX (4.4 x 10(-5) M) but inhibited dose-dependently by verapamil (5.1 and 51.0 x 10(-7) M).3 Adenosine-induced vascular relaxations were greatly increased in the presence of papaverine (6.1 x 10(-7) M) but significantly reduced in the presence of IBMX (4.4 x 10(-5) M) or verapamil (5.1 and 51.0 x 10(-7) M).4 The vasodilatation produced by isoprenaline was increased in the presence of IBMX (4.4 x 10(-5) M) or papaverine (6.1 x 10(-7) M), but inhibited by verapamil (5.1 and 51.0 x 10(-7) M).5 The vascular relaxant effects of nitroglycerine and papaverine were inhibited in the presence of IBMX (4.4 x 10(-5) M) or verapamil (5.1 and 51.0 x 10(-7) M). Papaverine (6.1 x 10(-7) M) also antagonized nitroglycerine-induced vascular relaxation.6 The vasodilator effect of IBMX was greatly reduced in the presence of papaverine (6.1 x 10(-7) M) or verapamil (5.1 and 51.0 x 10(-7) M).7 The vascular relaxant effect of verapamil was reduced proportionally by raising the extracellular Ca(2+) concentration from 1.25 to 5.0 mM while those elicited by histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX were not modified by this procedure.8 These results were taken as an indication that several vasodilators (e.g. histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX), but not a Ca(2+) antagonist such as verapamil, produce a fraction of their vasodilator effects by promoting Ca(2+) extrusion from and/or Ca(2+) sequestration into the vascular smooth muscle cells, via a cyclic adenosine 3',5'-monophosphate-dependent mechanism.