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

Ruboxistaurin is a selective protein kinase C β 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  μ g/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 (ΔsSBP/1n[GTN dose]) curve ( P =0.272 analysis of covariance) or affect the ΔsSBP 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. Clinical Pharmacology & Therapeutics (2007) 82 181–186. doi: 10.1038/sj.clpt.6100210 ; published online 18 April 2007