title: Sympathetic functions in NG-nitro-L-arginine-methyl-ester-induced hypertension: modulation by the renin-angiotensin system.
abstract: BACKGROUND
  Nitric oxide and angiotensin II have been shown to attenuate cardiac beta-adrenergic inotropism.
  
  
  OBJECTIVE
  To study sympathetic presynaptic and post-synaptic functions after chronic nitric oxide synthesis blockade with NG-nitro-L-arginine-methyl-ester (L-NAME, for 40 days) in association with renin-angiotensin system blockade (during the last 12 days) in order to evaluate the possible physiological interactions between these systems.
  
  
  METHODS
  Haemodynamic parameters in conscious rats were assessed. Release of noradrenaline from isolated atria and cardiac beta-adrenergic-adenylyl cyclase pathway in rats of sham-treated and L-NAME-treated groups, with or without losartan or enalaprilat treatment, were assessed.
  
  
  RESULTS
  L-NAME-treated rats developed a time-dependent increase in blood pressure associated with increased plasma adrenaline levels whereas plasma noradrenaline and cardiac catecholamine levels were similar to those in sham-treated rats. Field-stimulated release of noradrenaline, cardiac beta-adrenoceptor density and affinity and isoproterenol-stimulated formation of cyclic AMP were similar in sham and L-NAME-treated rats. However, Gpp(NH)p, NaF and forskolin-stimulated adenylyl cyclase activity were greater in L-NAME rats although Gs and Gi protein levels were similar in sham-treated and L-NAME-treated rats. Losartan and enalaprilat treatments exerted equipotent angiotensin-pressor response blockade and hypotensive effects whereas catecholamine levels were not altered. Interestingly, only losartan treatment acted to reduce the increased Gs-adenylyl cyclase activity in L-NAME rats, without alteration of G protein levels.
  
  
  CONCLUSIONS
  The nitric oxide synthase blockade-induced hypertension seems to be associated with increased adrenal-medullary system and renin-angiotensin system activities. The increased Gs-adenylyl cyclase activity after chronic inhibition of formation of nitric oxide suggests that nitric oxide plays a modulatory role in formation of cyclic AMP, to which angiotensin II seems to contribute through an angiotensin II type 1 receptor-mediated mechanism.
authors.affiliation: Research Group on the Autonomic Nervous System, Faculty of Medicine, Université de Montréal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: K-Laflamme
authors.forename: S
authors.initials: S
authors.lastname: Foucart
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: C
authors.initials: C
authors.lastname: Lambert
authors.forename: R
authors.initials: R
authors.lastname: Cardinal
authors.forename: J
authors.initials: J
authors.lastname: de Champlain
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D015773:Enalaprilat / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D019001:Nitric Oxide Synthase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015773:Enalaprilat; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D004837:Epinephrine