Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo

Abstract

0.03-300mgkg-1, i.v.) induced a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. 5L-NMMA, L-NIO and L-NAME (100 mgkg-',i.v.) inhibited significantly the hypotensive responses to ACh and bradykinin. 6 The increase in blood pressure and bradycardia produced by these compounds were reversed by L-arginine (30-100 mg kg-1, i.v.) in a dose-dependent manner. 7 All of these effects were enantiomer specific. 8 These results indicate that L-NMMA, L-NIO and L-NAME are inhibitors of NO synthase in the vascular endothelium and confirm the important role of NO synthesis in the maintenance of vascular tone and blood pressure.

Evidence That Acetylcholine Mediates Increased Cerebral Blood Flow Velocity in Crucian Carp through a Nitric Oxide—Dependent Mechanism

“…lA). L-NAME is a com petitive reversible inhibitor of NOS, although an excess of L-arginine appears to be needed to re move L-NAME from NOS in mammals (Rees et a!., 1990). Thus, it is possible that L-NAME more readily dissociates from NOS in fish than in mam mals.…”

Inhibition of airway smooth muscle tone by Chinese herbal medicines

“…Third, airway cells such as nerve fibres and epithelial cells are constitutively generating nitric oxide (NO) [19,20], which in turn inhibits bronchoconstrictor responses [21]. In the present study, because the effects of TJ-17 and TJ-23 were not altered by the specific nitric oxide synthetase (NOS) inhibitor L-NAME [16], the possibility that the herbal drugs could have stimulated the synthesis and/or release of NO can be excluded. Finally, pretreatment of tissues with Rp-cAMPS, a cAMP-dependent protein kinase inhibitor, or KT5823, a cGMPdependent protein kinase inhibitor [13], had no effect on the TJ-17-and TJ-23-induced inhibition, indicating that the involvement of these cyclic nucleotides is not likely.…”

“…mL -1 ) in the absence and presence of ouabain (1310 -7 M), a Na + -K + -ATPase inhibitor, or charybdotoxin (1310 -7 M), a Ca 2+ -activated K + channel blocker [13]. In addition, possible involvement of the generation of inhibitory prostaglandins [14], the release of nitric oxide [15], and the synthesis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were likewise assessed by the use of the following pharmacological blocking agents: indomethacin (3310 -6 M), a cyclooxygenase inhibitor; N G -nitro-L-arginine methyl ester (L-NAME, 1310 -3 M), an inhibitor of nitric oxide synthase [16]; adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS, 1310 -4 M), a specific inhibitor of cAMP-dependent protein kinase; and KT5823 (N-methyl-(8R*, 9S*, 11S*)-(-)-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H, 11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one, 2310 -6 M), a specific inhibitor of cGMP-dependent protein kinase [17].…”

Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254

“…Drinking water was removed from hyperosmotic rats for 3-4 h until sacrifice. To compare reductions in NADPH-d activity produced by PCB exposure to that produced by acute NOS blockade, a group of control hyperosmotic rats were injected with N G -nitro-Larginine-methyl ester (L-NAME), a general NOS inhibitor (Rees et al, 1990), at a dose of 50 mg/kg, i.p. at 30 min prior to and 1.5 h following the in vivo saline injection.…”