We sought to compare the sensitivity of endocardial and epicardial microvessels to several important neurohumoral substances. Porcine endocardial microvessels (86-200 microns diam) from the anterior papillary muscle and epicardial microvessels of similar size from the left anterior descending distribution were studied in a pressurized state using an in vitro microvessel-imaging apparatus. Endothelium-dependent relaxations to bradykinin, ADP, A23187, and to the endothelium-independent vasodilator nitroprusside were identical between endocardial and epicardial microvessels. In contrast, the sensitivity of endocardial microvessels to adenosine was substantially greater than that of epicardial microvessels (ED50s of -6.59 +/- 0.05 vs. -5.66 +/- 0.11, P less than 0.001, endocardial vs. epicardial, respectively), although adenosine caused 100% relaxation of both groups of vessels at the highest concentrations. Adenosine vasorelaxation was not affected by inhibition of cyclooxygenase by indomethacin (1 microM) or depletion of guanosine 3',5'-cyclic monophosphate by LY 83583 (1 microM). Forskolin dilated both endocardial and epicardial vessels completely but was more potent in endocardial vessels. These data show that endocardial and epicardial microvessels exhibit similar sensitivity to most vasodilator agents. Endocardial microvessels, however, are more sensitive to both adenosine and forskolin. The enhanced responsiveness to adenosine may be related to adenosine 3',5'-cyclic monophosphate-mediated mechanisms and may have important implications regarding regulation of myocardial perfusion in deeper subendocardial layers.
Regional Myocardial Function at the Papillary Muscle Insertion Site.
