Coronary vessels are squeezed by the surrounding myocardium during systole, impeding blood flow specifically in the subendocardium. To study the myocardial compression effect, we applied pulsatile transvascular pressure to isolated, cannulated subendocardial (Endo) and subepicardial (Epi) resistance arteries. Pressure pulsation at 0.5 to 2.5 Hz between 20 and 100 mmHg induced dilation of preconstricted vessels that was somewhat larger in Epi arterioles. In four Epi and five Endo arterioles loaded with fura 2, pulsation led to a small increase in intracellular calcium. Pulsation induced a significant decrease in IC(50) for bradykinin (BK) (5.9 +/- 0.6 vs. 27.3 +/- 3.2 nM in Epi vessels and 7.6 +/- 0.3 vs. 302 +/- 9 nM in Endo vessels), compared with steady pressure. The adenosine (Ado) sensitivity was not significantly affected (2.21 +/- 0.08 vs. 3.76 +/- 0.4 microM) in Epi arteries but was enhanced during pulsations in Endo vessels (3.1 +/- 0.3 vs. 10.1 +/- 0.6 microM). When pulsation-induced dilation was compensated by a higher concentration of the preconstrictor (U-46619), a significantly larger dilation to BK or Ado was found during pulsations. In conclusion, pulsation-induced dilation occurs at physiologically relevant frequencies and amplitudes in Endo vessels. The process does not involve intracellular calcium reduction and increases vasodilator sensitivity.