Intermittent hypoxia increases blood pressure in rats along with increased endothelin-1 constrictor sensitivity in a protein kinase Cδ (PKCδ)-dependent manner. Because phosphoinositide-dependent kinase-1 (PDK-1) regulates PKCδ, this study investigated the contribution of PDK-1 to hypoxia-induced hypertension. Inhibition of PDK-1 blunted endothelin-1 constriction in arteries from rats that had hypoxia-induced hypertension but not normal rats. In addition, treatment of rats with the PDK-1 inhibitor OSU-03012 [2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-acetamide], lowered blood pressure in hypertensive rats but not in rats with normal blood pressure. The results suggest that intermittent hypoxia unmasks a role for PDK-1 in regulating endothelin-1 constrictor sensitivity and blood pressure, suggesting that PDK-1 may be effective treatment of some types of hypertension.
See article at J Pharmacol Exp Ther 2013 344:68–76.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics