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Br J Pharmacol. 1993 December; 110(4): 1457–1464.
PMCID: PMC2175847
Regional and cardiac haemodynamic effects of NG, NG,dimethyl-L-arginine and their reversibility by vasodilators in conscious rats.
S. M. Gardiner, P. A. Kemp, T. Bennett, R. M. Palmer, and S. Moncada
Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
Abstract
1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG), sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and bradycardic effects, accompanied by renal, mesenteric and hindquarters vasoconstrictions. The magnitude and duration of these effects were similar for ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg-1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of its pressor and mesenteric and hindquarters haemodynamic effects, and reduced substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was almost as effective as SNP in reversing all these variables.(ABSTRACT TRUNCATED AT 250 WORDS)
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  • Boughton-Smith, NK; Hutcheson, IR; Deakin, AM; Whittle, BJ; Moncada, S. Protective effect of S-nitroso-N-acetyl-penicillamine in endotoxin-induced acute intestinal damage in the rat. Eur J Pharmacol. 1990 Dec 4;191(3):485–488. [PubMed]
  • de Wildt, DJ; Sangster, B. An evaluation of derived aortic flow parameters as indices of myocardial contractility in rats. J Pharmacol Methods. 1983 Aug;10(1):55–64. [PubMed]
  • Gardiner, SM; Compton, AM; Bennett, T; Hartley, CJ. Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats? Am J Physiol. 1990 Aug;259(2 Pt 2):H448–H456. [PubMed]
  • Gardiner, SM; Compton, AM; Bennett, T; Palmer, RM; Moncada, S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. [PubMed]
  • Gardiner, SM; Compton, AM; Kemp, PA; Bennett, T. Cardiac output effects of endothelin-1, -2 and -3 and sarafotoxin S6b in conscious rats. J Auton Nerv Syst. 1990 Jun;30(2):143–147. [PubMed]
  • Haywood, JR; Shaffer, RA; Fastenow, C; Fink, GD; Brody, MJ. Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol. 1981 Aug;241(2):H273–H278. [PubMed]
  • Ignarro, LJ; Lippton, H; Edwards, JC; Baricos, WH; Hyman, AL; Kadowitz, PJ; Gruetter, CA. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981 Sep;218(3):739–749. [PubMed]
  • Kowaluk, EA; Fung, HL. Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J Pharmacol Exp Ther. 1990 Dec;255(3):1256–1264. [PubMed]
  • Lopez-Belmonte, J; Whittle, BJ; Moncada, S. The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br J Pharmacol. 1993 Jan;108(1):73–78. [PubMed]
  • Moncada, S; Palmer, RM; Higgs, EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed]
  • Radomski, MW; Rees, DD; Dutra, A; Moncada, S. S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol. 1992 Nov;107(3):745–749. [PubMed]
  • Smith, TL; Hutchins, PM. Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension. 1979 1(5):508–517.Sep–Oct; [PubMed]
  • Smits, JF; Coleman, TG; Smith, TL; Kasbergen, CM; van Essen, H; Struyker-Boudier, HA. Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol. J Cardiovasc Pharmacol. 1982 4(6):903–914.Nov–Dec; [PubMed]
  • Vallance, P; Leone, A; Calver, A; Collier, J; Moncada, S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992 Mar 7;339(8793):572–575. [PubMed]