l‐NAME, nitric oxide and jejunal motility, blood flow and oxygen uptake in dogs

Abstract

1The effects of the inhibitor of nitric oxide (NO) synthesis, N0-nitro-L-arginine methyl ester (L-NAME), on systemic arteriil blood pressure and jejunal motility, blood flow, and oxygen uptake have been investigated in anaesthetized dogs. 2 L-NAME (cumulative doses of 0.1-20 mg kg-', i.v.) dose-dependently increased blood pressure and jejunal motility and decreased heart rate. The maximal response of these three variables occurred at doses, 3, 10 and 10mgkg-l, respectively. L-NAME (cumulative doses of 0.5-5mgkg-') also dosedependently induced jejunal vasoconstriction. The jejunal vascular resistance returned to control values as the cumulative doses reached 10 and 20 mg kg-', which corresponded to the maximal increase in jejunal motility. 3 A single intravenous injection of L-NAME (10mgkg-') produced a prompt increase in blood pressure, which lasted for at least 50min. 4 L-NAME (10 mg kg-') produced a progressive rise in jejunal motility reaching its maximum (47 ± 6 mmHg) 15 min after the administration, and lasting for 40-50 min. Both the basal lumen pressure and the amplitude of rhythmic contractions increased during this period. 5 L-NAME (10 mg kg-') produced a triphasic change in jejunal vascular resistance and blood flow measured by timed collection of venous outflow. The blood flow decreased initially (-43% at 5 min), increased (+ 35%) and returned to control value between 15 and 35 min, then decreased (-35%) 40-50 min post-infusion. Jejunal vascular resistance reflected the blood flow response (+ 88% at both 5 and 50 min). The time during which the reversal of the vasoconstriction occurred (15-35 min) corresponded to the time of marked increase in motility, and was accompanied by a significant increase in jejunal oxygen uptake (+ 18%). 6 The L-NAME-induced increase in motility was prevented by L-arginine (1 g kg-', i.v.) but not by D-arginine pretreatment. The interim (15-35 min) changes in jejunal blood flow, vascular resistance and oxygen uptake were also prevented by L-arginine pretreatment. 7 L-Arginine pretreatment attenuated L-NAME-induced hypertension for 5 min. 8 The L-NAME-induced increases in jejunal vascular resistance and motility were inhibited by either local intra-arterial infusion of L-arginine (32 mM local arterial blood concentration) or topical application of 2 gM nitroglycerin. Infusion of D-arginine (32 mM local arterial blood concentration) had no such effect. 9 The L-NAME-induced increase in blood pressure was not the mechanism by which jejunal motility was increased, because similar increases in blood pressure by mefenamate (10 mg kg-', i.v.) had no such effect. 10 Thus, inhibition of nitric oxide synthesis by L-NAME increased jejunal motility and vascular resistance and the marked increase in motility can abolish or reverse the vasoconstriction. Endogenous nitric oxide may play a role in regulating motility and blood flow in the resting canine jejunum.

Angiotensin-(1–7) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver

“…The vasodilatory effects of Ang- (1)(2)(3)(4)(5)(6)(7) are NOS and guanylate cyclase dependent. We then investigated the intracellular mechanisms that might be responsible for the effects of Ang-(1-7).…”

“…There was one additional group in which both AT1R and Mas receptor were blocked. The doses of lisinopril, candesartan, PD123319, JE049, A779, AVE0991, D-Pro 7 -Ang-(1-7), L-NAME, and ODQ were based on our laboratory's preliminary investigations and published studies (1,7,8,15,26,39,45,46). To determine whether Ang-(1-7) affected the response to another major mediator of hepatic vascular tone and to dissect out the involvement of AT1R in the Ang-(1-7) signaling pathway, we administered the ␣-adrenergic agonist MTX in two groups using the same design as for Ang II; one group of livers was perfused in the presence of the AT1R blocker candesartan and the other with candesartan plus the Mas receptor blocker A779.…”

“…It is now known that there is an alternate arm of the RAS in which ACE2, a homolog of ACE, degrades Ang II and generates angiotensin-(1-7) [Ang- (1)(2)(3)(4)(5)(6)(7)], which has a number of effects that appear to oppose those of Ang II. These effects are mediated in part by the Mas receptor, a novel endogenous G-protein-coupled receptor (GPCR) (14,22,24,34,40,47).…”

Characterization of 5-HT7-receptor-mediated gastric relaxation in conscious dogs

“…To assess this possibility, the influence of the NO synthase inhibitor L-NAME was investigated. A dose of L-NAME was chosen that has been previously shown to affect intestinal motility in dogs (2). The administration of L-NAME caused a decrease in gastric volume, reflecting a stomach contraction.…”

1a,25-Dihydroxycholecalciferol (Vitamin D3) Induces NO-Dependent Endothelial Cell Proliferation and Migration in a Three-Dimensional Matrix

“…It has been reported that this hormone decreases or has no effect on endothelium proliferation [6,11,12,13], but it can induce nitric oxide (NO) synthesis [4]. NO is endogenously synthesized from the guanidino nitrogen atoms of L-arginine or can be produced from exogenous sources, such as nitrovasodilatators by one of several isoforms of NO synthases (NOS) [14,15]. In the circulatory system, NO is produced by a constitutively-expressed endothelial NOS isoform (eNOS) and acts as an endogenous nitrovasodilatator [16] playing a pivotal role in EC function [17,18].…”