COMPARISON OF RESPONSES TO AMINOGUANIDINE AND N^ω‐NITRO‐L‐ARGININE METHYL ESTER IN THE RAT AORTA

Abstract

1. We have compared the effect of aminoguanidine with that of N omega-nitro-L-arginine methyl ester on isolated thoracic aortic rings obtained either from endotoxin (lipopolysaccharide, 10 mg/kg, i.v. for 3 h) or vehicle (saline) treated rats. 2. Administration of endotoxin for 3 h resulted in a hypotension and a significant reduction of pressor responses to norepinephrine (1 micrograms/kg, i.v.) in the anaesthetized rat. 3. In intact rings obtained from vehicle treated rats, aminoguanidine (0.3 and 1 mmol/L) had no significant effect on acetylcholine-induced relaxation (10(-9)-10(-5) mol/L), whereas N omega-nitro-L-arginine methyl ester (0.3 mmol/L and 1 mmol/L) abolished that response, suggesting that aminoguanidine does not inhibit the activity of constitutive nitric oxide synthase. 4. Relaxation induced by L-arginine (10(-6)-10(-2) mol/L) was competitively inhibited by both aminoguanidine (0.3 mmol/L) and N omega-nitro-L-arginine methyl ester (0.3 mmol/L) in endothelium-denuded aortic rings obtained from endotoxin treated rats. 5. Three hours of endotoxaemia was associated with an impairment of contraction to norepinephrine (10(-9)-10(-6) mol/L) in the endothelium-denuded aorta ex vivo. This hyporeactivity to norepinephrine was partially restored by treatment of the vessels either with aminoguanidine (0.3 mmol/L) or with N omega-nitro-L-arginine methyl ester (0.3 mmol/L) in vitro. 6. These results in isolated thoracic aortae of the rat reinforce that aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase, whereas N omega-nitro-L-arginine methyl ester is a non-selective inhibitor of both the inducible and constitutive nitric oxide synthase.

Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis

“…This vasorelaxation was significantly inhibited by removing of functional endothelium or pretreatment of l-NAME, a well-known non-selective nitric oxide synthase inhibitor (Yen et al, 1995). These results suggest that the vasorelaxation caused by EERSC may be mediated, at least in part, through endothelium-dependent nitric oxide signaling pathway.…”

Inducible Nitric Oxide Synthase and Blood Pressure

“…26,27 In situ, 0.1 to 1.0 mol/L aminoguanidine has no significant influence on the tone of aortic rings, whereas L-NAME and L-NMMA are potent constrictors in aortic rings from normal rats. 28,29 In vivo, aminoguanidine is 40 times less potent than L-NMMA to acutely increase blood pressure in rats. 30 These studies indicate that aminoguanidine can be used as a selective inhibitor of iNOS in vivo.…”

L‐NAME inhibits Mg2+‐induced rat aortic relaxation in the absence of endothelium

“…The induction of a Ca 2+ ‐dependent, dexamethasone‐insensitive iNOS by endotoxin or interleukin‐1 has been reported in rabbit articular chondrocytes (Palmer et al ., 1992) and activated rodent macrophages (Hiki et al ., 1991; Hecker et al ., 1992). Our contention that the ability of L ‐NAME to reverse Mg 2+ ‐induced relaxation in endothelium‐denuded aortic rings under our experimental conditions is unrelated to L ‐NAME‐sensitive iNOS in vascular smooth muscle is further supported by the inability of aminoguanidine pretreatment, which preferentially inhibits iNOS activity (Corbett et al ., 1992; Griffiths et al ., 1993; Joly et al ., 1994; Yen et al ., 1995), to counteract the reversal effect of L ‐NAME on Mg 2+ ‐induced relaxation. To date, there has been no precedence to demonstrate that Mg 2+ or any divalent cations could induce iNOS in smooth muscle of any type.…”