05, ANOVA; Fig. 1B). The effect of nilotinib, another tyrosine kinase inhibitor05, ANOVA; Fig. 1B).

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05, ANOVA; Fig. 1B). The effect of nilotinib, another tyrosine kinase inhibitor
05, ANOVA; Fig. 1B). The impact of nilotinib, yet another tyrosine kinase inhibitor, around the ICP/ MAP ratio is shown in Figure 1C. The IC injection of nilotinib in doses of ten mg/kg made dose-related increases in the ICP (11 two to 40 5; P .05, ANOVA), ICP/MAP ratio (0.20 0.01 to 0.49 0.07; P .05, ANOVA; Fig. 1C), and AUC (1213 446 to 5397 867; P .05, ANOVA). The increases in ICP in response to the IC injection of imatinib and nilotinib have been rapid in onset, ranging from 15 to 30 seconds. Really little delay was seen inside the lower within the MAP in response towards the IC injection of imatinib (Fig. 1D,E). The time course with the improve inside the ICP and decrease inside the MAP in response to the IC injection of imatinib 10 mg/kg was similar (Fig. 1D,E). These data indicate that the tyrosine kinase inhibitor had important erectile and systemic hypotensive activity in the rat. The role of NOS and NO in mediating the erectile response to imatinib was also investigated. Immediately after therapy with all the NOS inhibitor L-NAME 50 mg/kg IV, a dose that Plasmodium Source inhibited the enhance in ICP in response to cavernosal nerve stimulation by 85 (67 four vs 12 three mm Hg; P .05, paired t test), the increase in the ICP and AUC in response towards the IC injection of imatinib soon after L-NAME remedy was not MMP-14 Purity & Documentation altered compared using the responses inside the manage rats (P .05 for all doses, paired t test; Fig. 2A). The impact of cavernosal nerve crush injury on the response to imatinib was also investigated. The boost inside the ICP in response to the IC injection of imatinib ten mg/kg was not altered by the nerve crush injury, which decreased the response to cavernosal nerve stimulation at 16 Hz by 92 (64 3 vs 5 1 mm Hg; P .05, paired t test; Fig. 2B). The results of these experiments indicate that the increase in the ICP in response to IC injection of imatinib was not dependent on NOS or NO release or tonic nerve activity in the cavernosal nerves. The IC injection of imatinib decreased the MAP at all doses studied. Also, the systemic vascular effects with the tyrosine kinase inhibitor were investigated in experiments in which IV imatinib was injected. In these experiments, the cardiac output was measured plus the systemic vascular resistance determined. The IV injection of imatinib in doses of 0.30 mg/ kg created dose-related decreases within the MAP (5 1 to 53 2 mm Hg; P .05, ANOVA) devoid of causing substantial alterations in cardiac output (P .05, ANOVA; Fig. 3A). TheUrology. Author manuscript; offered in PMC 2014 July 01.Pankey et al.Pagesystemic vascular resistance decreased 2 8 at imatinib doses of 0.30 mg/kg (P .05, ANOVA; Fig. 3A). The decreases in systemic arterial stress and systemic vascular resistance in response to IV injection of imatinib were not altered by administration of LNAME 50 mg/kg IV (P .05, paired t test; Fig. 3A,B). The results of those research indicate that imatinib has marked vasodilator activity which is not dependent on NO within the systemic vascular bed. The erectile and systemic responses to imatinib and the NO donor SNP have been compared (Fig. 4). Imatinib was four orders of magnitude less potent than SNP in its ability to increase the ICP when injected IC (Fig. 4A). Nonetheless, it had efficacy similar to that of SNP simply because each agents at the highest doses studied elevated the ICP by roughly 50 mm Hg (Fig. 4A). Imatinib was around three orders of magnitude less potent than SNP in its ability to lower the MAP when injected IV but had similar efficacy for the reason that both agents decrease.