Key result
PKC inhibition prevents a ~5-fold drop in nitroglycerin sensitivity during chronic nitrate therapy.
Why the study?
The role of protein kinase C activation in the development of vascular nitroglycerin tolerance was investigated to identify potential prevention strategies.
Does the specific PKC inhibitor N-benzoyl-staurosporine prevent the development of vascular tolerance to nitroglycerin in male Wistar rats?
Does the specific PKC inhibitor N-benzoyl-staurosporine prevent the development of vascular tolerance to nitroglycerin in male Wistar rats?
Effect estimate: 5.5 fold decrease in NTG-sensitivity in controls
In vivo inhibition of protein kinase C prevents the development of vascular nitroglycerin tolerance in a rat model.
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May limit chronic NTG utility in patients; leaves open PKC inhibition to prevent tolerance pending clinical trials.
Zierhut et al. (1996) studied Vascular nitroglycerin tolerance. N-benzoyl-staurosporine (PKC inhibitor) vs. Vehicle (controls) was evaluated on Sensitivity of aortic rings to NTG (5.5 fold decrease in NTG-sensitivity in controls). Simultaneous in vivo administration of the specific PKC inhibitor N-benzoyl-staurosporine prevented the 5.5-fold decrease in NTG sensitivity induced by chronic NTG infusion in rats.
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