Studies on the mechanism of action of various vasodilators

摘要

>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 Ca²⁺ antagonist.>2 The vasodilator effect of histamine was potentiated by papaverine (6.1 × 10^-7 M) and IBMX (4.4 × 10^-5 M) but inhibited dose-dependently by verapamil (5.1 and 51.0 × 10^-7 M).>3 Adenosine-induced vascular relaxations were greatly increased in the presence of papaverine (6.1 × 10^-7 M) but significantly reduced in the presence of IBMX (4.4 × 10^-5 M) or verapamil (5.1 and 51.0 × 10^-7 M).>4 The vasodilatation produced by isoprenaline was increased in the presence of IBMX (4.4 × 10^-5 M) or papaverine (6.1 × 10^-7 M), but inhibited by verapamil (5.1 and 51.0 × 10^-7 M).>5 The vascular relaxant effects of nitroglycerine and papaverine were inhibited in the presence of IBMX (4.4 × 10^-5 M) or verapamil (5.1 and 51.0 × 10^-7 M). Papaverine (6.1 × 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 × 10^-7 M) or verapamil (5.1 and 51.0 × 10^-7 M).>7 The vascular relaxant effect of verapamil was reduced proportionally by raising the extracellular Ca²⁺ 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 Ca²⁺ antagonist such as verapamil, produce a fraction of their vasodilator effects by promoting Ca²⁺ extrusion from and/or Ca²⁺ sequestration into the vascular smooth muscle cells, via a cyclic adenosine 3′,5′-monophosphate-dependent mechanism.