L-arginine availability determines the duration of acetylcholine-induced systemic vasodilatation in vivo

Aisaka, Kazuo; Gross, Steven S.; Griffith, Owen W.; Levi, Roberto

doi:10.1016/0006-291x(89)92281-x

Cited by 127 publications

(88 citation statements)

References 21 publications

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“…For example, in anaesthetized guinea-pigs (Aisaka et al, 1989) and rats (Rees et al, 1990), as well as in conscious rats (Gardiner et al, 1990ab,c), administration of L-NMMA or L-NAME consistently induced hypertension, but did not markedly affect the maximal hypotensive response to intravenously administered acetylcholine, although the L-arginine analogues tended to reduce the duration of this hypotensive phase. Furthermore, in conscious rats, the regional (renal, mesenteric and hindquarter) vasodilator effects of acetylcholine were not markedly affected by L-NAME (Gardiner et al, 1990c).…”

Section: Discussionmentioning

confidence: 99%

“…Several hypotheses were advanced to explain this lack of inhibition in vivo; one possibility is that, in vivo, the vasodilator response to acetylcholine, as well as that to other endothelium-dependent vasodilators (e.g. bradykinin), is partly nitric oxide-independent (Gardiner et al, 1990c), or is mediated through the release of nitric oxide from intracellular stores that do not rely on mobilization of L-arginine (Aisaka et al, 1989). In this regard, the fact that, in the presence of L-NMMA or L-NAME, the peak hypotensive response to acetylcholine was not affected, but the duration of acetylcholine-induced hypotension was reduced (Aisaka et al, 1989;Rees et al, 1990), would suggest that acetylcholineinduced vasodilatation is the result of two events: (1) an initial vasodilatation which depends on the release of NO or an NO-like molecule (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…bradykinin), is partly nitric oxide-independent (Gardiner et al, 1990c), or is mediated through the release of nitric oxide from intracellular stores that do not rely on mobilization of L-arginine (Aisaka et al, 1989). In this regard, the fact that, in the presence of L-NMMA or L-NAME, the peak hypotensive response to acetylcholine was not affected, but the duration of acetylcholine-induced hypotension was reduced (Aisaka et al, 1989;Rees et al, 1990), would suggest that acetylcholineinduced vasodilatation is the result of two events: (1) an initial vasodilatation which depends on the release of NO or an NO-like molecule (e.g. S-nitrosothiol; Myers et al, 1990) from a preformed endothelial pool, and (2) a sustained vasodilator phase which depends on the biosynthesis of nitric oxide from L-arginine.…”

Section: Discussionmentioning

confidence: 99%

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Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open‐chest dogs

Richard

Berdeaux

Rochelle

et al. 1991

British J Pharmacology

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1 The role of endothelial nitric oxide synthesis from L-arginine in the regulation of coronary vascular tone and myocardial tissue perfusion was evaluated in anaesthetized, open-chest dogs. Coronary blood flow was measured with an electromagnetic flow probe placed around the left circumflex coronary artery. Coronary vascular resistance was calculated from mean arterial blood pressure and mean coronary blood flow, whereas regional myocardial tissue flow was determined by use of the radioactive microspheres technique. 2 NG-monomethyl L-arginine (L-NMMA) and N0-nitro-L-arginine methyl ester (L-NAME), administered directly into the left circumflex artery, induced a small increase in arterial blood pressure and an increase in coronary vascular resistance. However, myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural), was unaffected by L-NMMA or L-NAME. 3 Acetylcholine, administered intracoronarily, induced an increase in left circumflex coronary blood flow and a decrease in coronary vascular resistance, without affecting systemic haemodynamics. This coronary vasodilator effect of acetylcholine was markedly inhibited by L-NMMA and L-NAME, the latter being a more potent antagonist than the former. 4 These results indicate that the endothelial L-arginine pathway is largely responsible for the coronary vasodilator effect of acetylcholine. However, although basal release of nitric oxide from L-arginine apparently contributes to the regulation of resting coronary vascular tone, blockade of this pathway does not affect myocardial tissue perfusion, possibly because of compensatory mechanisms occurring at the level of small arterioles and/or capillaries.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open‐chest dogs

Richard

Berdeaux

Rochelle

et al. 1991

British J Pharmacology

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“…As a consequence, the level of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in smooth muscle cells increases, leading to smooth muscle relaxation (Rapoport and Murad, 1983;Ignarro, 1989;Moncada et al, 1991). The synthesis of EDNO can be blocked by L-arginine analogues such as N ω -nitro-L-arginine (L-NOARG), N G -monomethyl-L-arginine or N ω -nitro-Larginine methyl ester (L-NAME) (Palmer et al, 1988;Moore et al, 1990;Rees et al, 1990), and the acute administration of these inhibitors of NOS to animals causes elevation of blood pressure (Aisaka et al, 1989;Gardiner et al, 1990a and1990b;Moncada et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Sekiguchi

Yamamoto

Matsuda

et al. 2002

J. Smooth Muscle Res.

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To evaluate whether the elevated blood pressure induced by chronic treatment with N ω -nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endotheliumdependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N ω -nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

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“…NO is derived from a novel biosynthetic pathway involving the oxidation of a gua nidino nitrogen of L-arginine (6)(7)(8). Recently, it was reported that NG-monomethyl-L arginine (L-NMMA) competitively inhibits the generation of NO from L-arginine (8,9). Thus, L-NMMA can be utilized as a tool to selectively inhibit NO production.…”

mentioning

confidence: 99%

Pressor Effect of NG-Monomethyl-L-Arginine in SHRSP

Aisaka¹,

Mitani

Kitajima

et al. 1990

Japanese Journal of Pharmacology

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Abstract-Pressor effects of NG-monomethyl-L-arginine (L-NMMA), a selective inhibitor of nitric oxide production from L-arginine, on mean blood pressure (MBP) were investigated in conscious Wistar Kyoto rats (WKY) and stroke-prone spon taneously hypertensive rats (SHRSP). L-NMMA (0.1-10 mg/kg, i.v.) elicited a dose-dependent increase in the MBP of WKY and SHRSP. The pressor response to L-NMMA was more marked in SHRSP than in WKY. These results suggest that nitric oxide may play an important role in the blood pressure regulation in the conscious SHRSP.

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L-arginine availability determines the duration of acetylcholine-induced systemic vasodilatation in vivo

Cited by 127 publications

References 21 publications

Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open‐chest dogs

Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open‐chest dogs

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

Pressor Effect of NG-Monomethyl-L-Arginine in SHRSP

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