Inhibition Of Pkc Beta By Ruboxistaurin (Rbx) Does Not Enhance The Blood Pressure (Bp) Response To Glyceryl Trinitrate (Gtn).

Background Activation of PKC β by hyperglycemia impairs endothelial- and nitric oxide (NO)-dependent vasodilation. RBX, a specific inhibitor of PKC β undergoing clinical testing for the treatment of diabetic microvascular complications, normalizes NO signaling in diabetic animals and restores vascular function. This study assessed a possible interaction between RBX and the exogenous NO donor, GTN, on BP. Methods A randomized, double masked, placebo (PL)-controlled, 2 period crossover study was performed in 21 stable angina pectoris subjects. RBX (96 mg/d; 3x the therapeutic dose) or PL was given orally to steady state. Graded GTN was then infused with dose escalation until discontinued for hypotension or when 120 mcg/min was achieved. Primary treatment comparison was the slope of the change in standing systolic BP from predose (ΔSSBP)/ ln(GTN dose) curve. Treatment difference in ΔSSBP at a GTN rate producing a 10 mmHg fall with PL treatment (GTN*) was also assessed. Results RBX did not alter the slope of ΔSSBP/ ln(GTN dose) curve (p=0.272 ANCOVA) or affect the ΔSSBP at the 8.44 mcg/min GTN* rate (mean −0.9 mmHg; 95% CI −3.3, 1.5). Conclusion Ruboxistaurin can be coadministered with organic nitrates as it does not potentiate their BP lowering effect. Clinical Pharmacology & Therapeutics (2005) 77, P15–P15; doi: 10.1016/j.clpt.2004.11.060