Vessel-specific role of sphingosine kinase 1 in the vasoconstriction of isolated basilar arteries.

Sphingosine-1-phosphate (S1P) constricts cerebral arteries through S1P(3) receptor stimulation. Because the activity of the key S1P-synthesizing enzyme, sphingosine kinase (SPK), can be stimulated by agonists of various G protein-coupled receptors, it is likely that S1P also acts as a second messenger for other vasoconstrictors. We investigated the effect of SPK inhibitors and SPK gene deletion on the contractile responses of isolated vessels to vasoactive agonists and KCl-induced depolarization.

Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms.

Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis.

Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension.

Hypertension and cardiac remodeling are associated with myocardial fibrosis, left ventricular (LV) hypertrophy, and diastolic heart failure. Fenofibrate suppresses aldosterone-mediated increases in myocyte matrix metalloproteinase activity and extracellular signal-regulated kinase phosphorylation. It is unknown whether the peroxisome proliferator-activated receptor-alpha agonist, fenofibrate, improves cardiac remodeling in a model of aldosterone-induced hypertension and LV hypertrophy.