Role of L-arginine-derived nitric oxide in cholinergic dilation of gastric arterioles

Abstract

The role of L-arginine-derived nitric oxide (NO) in cholinergic vasodilation of resistance vessels was studied in the intact stomach of the rat, utilizing an in vivo microscopy technique. Two L-arginine analogues, NG-monomethyl-L-arginine (L-NMMA) and nitro-L-arginine methyl ester (L-NAME), were used to block NO synthesis. Cholinergic dilation of gastric submucosal arterioles was induced by topical application of various concentrations of acetylcholine (ACh) (10(-7)-10(-4) M). Intravenous but not topical administration of L-NMMA and L-NAME caused an increase in arterial pressure. Intravenous or topical L-NAME reduces resting arteriolar diameter. These findings support the contention that NO formation modulates basal vascular tone and suggest that NO release may play a significant role in the regulation of the gastric circulation. L-Arginine analogues attenuated the arteriolar dilating effect of ACh but not adenosine or nitroglycerin. Substantial arteriolar responses to ACh remained after systemic or topical treatment with either L-NMMA or L-NAME. These results indicate that the L-arginine-NO pathway accounts only in part for ACh-induced vasodilation in gastric resistance vessels in vivo.

Heme oxygenase 2: endothelial and neuronal localization and role in endothelium-dependent relaxation.

“…vessels, especially those of smaller diameter, relaxation following muscarinic cholinergic stimulation is resistant to reversal by L-NAME (31,32). In these systems, CO may play a more prominent role as a mediator of blood vessel relaxation.…”

Gastrointestinal Function Regulation by Nitrergic Efferent Nerves

“…In anesthetized rats (Pique et al, 1989;Tepperman and Whittle, 1992;Chen et al, 1993;Pawlik et al, 1995) and cats (Macedo and Lautt, 1997) and in awake rats (Greenblatt et al, 1993), L-NA, L-NAME, or L-NMMA decreased gastrointestinal mucosal blood flow and increased vascular resistance, despite an increase in systemic blood pressure. In rats with stress-induced gastric injury, pretreatment with NO donors resulted in reduction of gastric lesions, increase in gastric blood flow, and increase in superoxide dismutase activity, suggesting that suppression of reactive oxygen species plays an important role in the action of NO donors (Kwiecien et al, 2002).…”

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…In anesthetized rats, intravenous or topical application of NOS inhibitors induced a fall in the resting gastric mucosal blood flow and vasoconstriction of gastric arterioles (Pique et al, 1989;Tepperman and Whittle, 1992;Chen et al, 1993). NO seems to function as a local vasodilator in the gastric mucosal microvasculature, although the relative contributions of neurogenic and endothelial NO have not been determined.…”