Pharmacological differentiation between large and small coronary vessels.

It has been reported that there are striking differences between large and small coronary arteries in their responsiveness to adenosine, nitroglycerin and catecholamines. The differential pharmacological responsiveness indicates differences in their excitation-contraction coupling mechanisms. Therefore, agents such as lyotropic anions (SCN-, NO3-, CH3SO4-) known to modulate these processes, and which by themselves do not have an inotropic effect, would be expected to differentially modulate the action of these substances on large and small coronary vessels. To test this hypothesis we studied the modulation by lyotropic anions of the effects of adenosine, nitroglycerin and verapamil on large and small intramural (0.5-0.6 mm diameter) dog coronary arteries. We have confirmed that small vessels are more sensitive to adenosine and verapamil and less sensitive to nitroglycerin than are large vessels. Replacement of Cl- by the lyotropic anions diminished the relaxing effects of adenosine in small vessels with the following order of potency, SCN- greater than NO3- greater than CH3SO4- greater than Cl-. NO3-. Replacement of Cl- resulted in almost total blockade of the adenosine response in small coronary arteries, whereas in large coronary vessels, the effects of nitroglycerin were reduced only 30%. The effects of verapamil in small vessels were slightly depressed whereas in large vessels its effects were unchanged. Our results further confirm that there are marked differences between the pharmacological responsiveness of large and small coronary vessels, indicating that these differences reside in the nature of their mechanisms controlling Ca++ translocation.