CLINICS 2011;66(8):1407-1411 Hemodynamic response to intrathecal sildenafil Bombarda G et al. Figure 1 - Time course of the mean arterial pressure (D MAP) and heart rate (D HR) induced by the intrathecal administration of 100 mg (A), 10 mg (B), 1 mg (C), or 0.1 mg (D) sildenafil or the vehicle (DMSO). *p,0.05 compared to DMSO. Effects of intrathecal administration of 8-bromo- cGMP on the MAP and HR. The intrathecal administration of different doses of the membrane-permeable analogue of cGMP, 8-bromo-cGMP or its vehicle, DMSO, did not affect the MAP or HR (Figure 2). Effects of intrathecal administration of forskolin and dibutyryl-cAMP on the MAP and HR. The administration of forskolin did not affect the MAP but did increase the HR, while the membrane-permeable cAMP analog, dibutyryl-cAMP, induced a rapid and significant increase in both the MAP and HR (Figure 3). DISCUSSION The major findings of this study indicate that the intrathecal administration of sildenafil in conscious rats results in a dose-dependent increase in the MAP combined with tachycardia that is unrelated to cGMP action as the administration of a cGMP analog (8-bromo-cGMP) had no effect. In addition, a direct activator of adenylate cyclase (forskolin) increased the HR but did not affect the MAP. In contrast, a cAMP analog (dibutyryl-cAMP) increased the MAP and HR, similar to the increase observed following the administration of 100 mg sildenafil. One possible explanation for the results observed follow- ing the intrathecal administration of sildenafil is the activation of SPNs located in the intermediolateral column of the spinal cord that predominantly innervate the heart and blood vessels. The hemodynamic response obtained with 10 and 1 mg of sildenafil indirectly support this hypothesis, as the increase in the MAP and HR was delayed when compared to results observed after the administration of 100 mg of the drug. The magnitude of the hemodynamic response was comparable even though the doses differed. A possible explanation for this delay may be that lower doses 1409