Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats

Abstract

is a multifunctional protein that is found in milk, neutrophils, and other biological fluids. Under inflammatory conditions, LF production is increased in the periphery by neutrophils. However, the cardiovascular function of LF is still unknown. In the present study, we investigated the effect of bovine LF (BLF) on the mean blood pressure (MBP) and heart rate (HR) in urethane-anesthetized rats and the vascular function of BLF in the rat thoracic aorta. Intravenous injection of BLF produced dose-dependent decreases in MBP but did not affect HR, while the opioid agonist morphine decreased both MBP and HR. The hypotensive effect of BLF was not altered by naloxone methiodide, which cannot pass through the blood-brain barrier, but was significantly reduced by naloxone hydrochloride, which does pass through the blood-brain barrier. BLF-induced hypotension was completely blocked by the NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) but not by the inactive enantiomer of L-NAME, N G -nitro-D-arginine methyl ester (D-NAME). BLF-induced hypotension was not altered by the muscarinic ACh receptor antagonist atropine or the cyclooxygenase inhibitor diclofenac. BLF produced relaxation in endothelium-intact but not endothelium-denuded aortic rings precontracted with phenylephrine. The relaxation evoked by BLF was completely blocked by L-NAME but not by D-NAME or the ATP-sensitive potassium channel blocker glibenclamide. These results suggest that BLF causes hypotension via an endothelium-dependent vasodilation that is strongly mediated by NO production and that BLF-induced hypotension also may be mediated by the central opioidergic system.

Protective Effect of Lactoferrin on Cisplatin-Induced Nephrotoxicity in Rats

“…In our study, urine volume increased up to 2.5 times higher than the basal volume when the rat received bLf at a dose of 30 mg/kg. Hayashida et al [11] reported that bLf causes a nitric oxide (NO)-dependent relaxation of smooth muscle in the rat's aorta, suggesting that bLf can affect the blood circulation in individual organs. The involvement of NO in the renoprotective effect in cisplatin-injected rats was supported by a treatment with L-arginine resulting in NO modulation [22].…”

Association of Circulating Lactoferrin Concentration and 2 Nonsynonymous LTF Gene Polymorphisms with Dyslipidemia in Men Depends on Glucose-Tolerance Status

“…There is evidence that lactoferrin increases nitric oxide production (25 ). In fact, lactoferrin has been shown to affect peripheral opioid-mediated antinociception via nitric oxide (26,27 ).…”

Whey beverages decrease blood pressure in prehypertensive and hypertensive young men and women

“…Whey contains lactoferrin, an antioxidant and antiinflammatory iron binding protein (Conneely, 2001). Hayashida et al (2004) reported that lactoferrin consumption in rats results in hypotension. The BP decrease was through an endotheliumdependent vasodilation mediated by nitric oxide production and possibly via the central opioidergic system.…”