BACKGROUND Although abnormal L-arginine NO signaling contributes to endothelial dysfunction in the aging cardiovascular system, the biochemical mechanisms remain controversial. L-arginine, the NO synthase (NOS) precursor, is also a substrate for arginase. We tested the hypotheses that arginase reciprocally regulates NOS by modulating L-arginine bioavailability and that arginase is upregulated i...

In this study we characterized the effects of the protein phosphatase (PP) type 1 and type 2A inhibitor cantharidin (Cant) and its structural analogs cantharidic acid and endothall on PP activity, force of contraction, and myosin light chain phosphorylation in rat aorta. All compounds inhibited PP activity in homogenates of rat aorta with a rank order of potency of Cant = cantharidic acid > end...

BACKGROUND Tissues respond to injury by releasing acute phase reaction (APR) proteins which regulate inflammation and angiogenesis. Among the genes upregulated in wounded tissues are tumor necrosis factor-alpha (TNFα) and the acute phase reactant orosomucoid-1 (ORM1). ORM1 has been shown to modulate the response of immune cells to TNFα, but its role on injury- and TNFα-induced angiogenesis has ...

BACKGROUND The mechanisms of amino-amide local anesthetic agent-induced vasoconstriction remain unclear. The current study was designed to examine the roles of the protein kinase C (PKC), Rho kinase, and p44/42 mitogen-activated protein kinase (p44/42 MAPK) signaling pathways in calcium (Ca2+)-sensitization mechanisms in ropivacaine-induced vascular contraction. METHODS Endothelium-denuded ra...

AIM In endothelium-denuded arteries, the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) induced a persistent hypo-reactivity to vasoconstrictors, and low-molecular weight thiols such as N-acetyl cysteine (NAC) produced a relaxant effect. These effects were attributed to the formation of vascular NO stores. In arteries with a functional endothelium, such long-lasting effects on arterial ton...

Presumably, the vasorelaxant properties of phosphodiesterase type 5 (PDE5) inhibitors are similar in isolated blood vessels. We aimed to explore the mechanisms underlying the vasorelaxation induced by the selective PDE5 inhibitors sildenafil, vardenafil, and tadalafil in the rat aorta. Aortic rings were mounted in 5-ml organ baths, and concentration-response curves for PDE5 inhibitors (0.0001-1...

Acrolein is a highly reactive aldehyde pollutant and an endogenous product of lipid peroxidation. Increased generation of, or exposures to, acrolein incites pulmonary and vascular injury. The effects of acrolein on the vasomotor responses of rat aortic rings were studied to understand its mechanism of action. Incubation with acrolein (10-100 microM) alone did not affect the resting tone of aort...

Rat aortic endothelium is differentiated regionally for three signal pathways capable of regulating the cGMP content of the underlying smooth muscle. Formation of nitric oxide (NO) from L-arginine and of glutamate from L-leucine increase cGMP; however, formation of prostaglandin H2 (PGH2) decreases cGMP. All three have peak activity in the windkessel area just distal to the aortic arch and decr...

These studies test the hypothesis that l-glutamine at its physiological plasma concentration, approximately 0.5 mM, can increase tissue content and net synthesis of glutamate in rat aortic segments in vitro, thereby mediating relaxation of the underlying smooth muscle in the elastic reservoir region of the thoracic aorta. Aortic segments were incubated in an isotonic medium with and without 21 ...

Chromosomal substitution strains afford the opportunity to discover regions of the rat genome that contain genes related to cardiovascular traits with the long-range goal of linking these genes to physiological function. PhysGen (Programs for Genomic Applications) created a consomic panel of rats derived from the introgression of a single chromosome (> or =95% of the BN chromosome, one at a tim...