CLINICS 2011;66(8):1407-1411 cardiovascular effects of sildenafil. Uckert et al.14 observed that both forskolin and sildenafil administered indepen- dently caused the relaxation of isolated human corpus cavernosum tissue. However, this effect was reversed by PKA-I (a cAMP-dependent kinase inhibitor) and PKG-I (a cGMP-dependent kinase inhibitor) in both cases. These findings suggest that cross-regulation may exist between the cyclic nucleotides cAMP and cGMP. The results of the current study are in line with those of Stief et al.,24 who observed that the administration of increasing concentra- tions of sildenafil in isolated human corpus cavernosum tissue did not modify the cGMP levels in the tissue, although it did increase the cAMP levels. Similarly, increasing concentrations of sildenafil administered to isolated human heart muscle did not alter the cGMP levels, although an increase in the cAMP levels was evident.24 In addition, the findings of Stief et al.24 demonstrate that milrinone, a PDE3-specific inhibitor, causes an increase in the intracellular cAMP levels without altering the cGMP levels, as PDE3 preferentially degrades cAMP. In addition, Botha et al.25 verified that while the serum levels of cAMP increase after the administration of two different doses of sildenafil and milrinone, the serum levels of cGMP are not altered. Overall, the results of the current study strongly suggest that the pressor response and tachycardia observed after the intrathecal administration of sildenafil to conscious rats involves the inhibition of non-PDE5, cAMP-increasing phosphodiesterases that activate sympathetic preganglionic neurons. 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