title: Vagotomy reveals the importance of the imidazoline receptors in the cardiovascular effects of marsanidine and 7-ME-marsanidine in rats.
abstract: BACKGROUND
  The recently synthesized novel benzazole derivates - marsanidine (1-[(imidazolidin-2-yl)imino]indazole) and 7-Me-marsanidine (1-[(imidazolidin-2-yl)imino]-7-methylindazole) display promising effects on the circulatory system. We previously indicated that i.v. administration of both compounds decreased the mean arterial blood pressure (MAP) and heart rate (HR) in rats. The cardiovascular effect of the tested compounds may consist not only in inhibiting the sympathetic, but also in activating the parasympathetic pathways related to vagal nerves. Present experiments were performed to determine how vagotomy, with or without an α2 adrenoreceptor blockade, may affect hypotensive and HR limiting actions of marsanidine and 7-Me-marsanidine.
  
  
  METHODS
  Both compounds were infused i.v. (10 μg/kg b.w.) to anesthetized rats, half of which underwent vagotomy. Half the intact, and half the vagotomised rats received RX821002, an α2 adrenorereceptor inhibitor. MAP and HR were monitored directly throughout the experiment.
  
  
  RESULTS
  Vagotomy enhanced hypotension observed after marsanidine administration. The α2 adrenergic blockade abolished the action of marsanidine in both the intact and vagotomised rats. Vagotomy did not affect the 7-Me-marsanidine-induced decrease of MAP or HR. However, it abolished the reducing effect of the α2 adrenergic receptor blockade on the hypotension triggered by 7-Me-marsanidine.
  
  
  CONCLUSIONS
  The results show that although cardiovascular effects of marsanidine and 7-Me-marsanidine are not mediated by the vagal nerves, vagotomy enhanced sensitivity of the sympathetic pathways for the tested compounds. While the action of marsanidine in vagotomised and intact rats may be explained by activation of the α2 adrenoreceptors, the effects of 7-Me-marsanidine seem to be α2 adrenoreceptor-independent. It seems likely that activation of I1 imidazoline receptors could mediate the observed effects.
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: kboblewski@gumed.edu.pl.
authors.forename: Konrad
authors.initials: K
authors.lastname: Boblewski
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Lehmann
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Sączewski
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Anita
authors.initials: A
authors.lastname: Kornicka
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Apolonia
authors.initials: A
authors.lastname: Rybczyńska
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D048289:Imidazolidines / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000187:drug effects / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D014628:Vagotomy
chemical_list: C531077:1-((imidazolidin-2-yl)imino)-7-methylindazole; C531076:1-((imidazolidin-2-yl)imino)indazole; D058669:Adrenergic alpha-2 Receptor Antagonists; D048289:Imidazolidines; D054755:Imidazoline Receptors; D007191:Indazoles; D018341:Receptors, Adrenergic, alpha-2; C410887:imidazoline I1 receptors; C058525:2-methoxyidazoxan; D019329:Idazoxan
keywords: Hypertension; I(1) imidazoline receptors; Imidazoline compounds; Vagotomy; α(2) Adrenoreceptors