Inhibition of PKC β by Ruboxistaurin Does Not Enhance the Acute Blood Pressure Response to Nitroglycerin

Ruboxistaurin is a selective protein kinase C beta inhibitor undergoing clinical investigation for treatment of diabetic microvascular complications. This study assessed a possible blood pressure (BP) interaction between ruboxistaurin and the exogenous nitric oxide donor, glyceryl trinitrate (GTN). Subjects (N=22) with chronic stable angina received placebo or ruboxistaurin 96 mg/day orally to steady state in a crossover design. Graded GTN (0, 5, 10, 20, 40, 80, and 120 microg/min) or 5% dextrose solution was then infused intravenously and BP was measured following each dose. Ruboxistaurin did not alter the slope of change in standing systolic BP (DeltasSBP/1n[GTN dose]) curve (P=0.272 analysis of covariance) or affect the DeltasSBP at the estimated GTN dose producing a 10-mm Hg reduction in sSBP from baseline on placebo (mean difference -0.9 mm Hg; 95% confidence of interval, -3.3-1.5). In conclusion, ruboxistaurin does not potentiate the acute BP-lowering effects of GTN.