title: Differential regulation of atrial contraction by P1 and P2 purinoceptors in normotensive and spontaneously hypertensive rats.
abstract: In the normotensive rat atrium, adenosine-5'-triphosphate and uridine-5'-triphosphate exert a biphasic effect consisting of an initial negative inotropic effect (NIE) followed by a subsequent positive inotropic effect (PIE). We comparatively studied these responses in normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Compared with NWRs, the NIE responses in the atria were lower and the PIE responses were higher in SHRs. The P1 purinoceptor antagonist, D 8-cyclopentyl-1,3-dipropylxanthine, partially blocked the NIE responses of both ATP and UTP and mildly enhanced the PIE responses in both NWRs and SHRs. Furthermore, the P2 purinoceptor blockers suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt induced a pronounced block of the PIE responses in both atria types. The PIE responses to ATP were inhibited more efficiently by nifedipine. These responses were depressed by ryanodine and, to a lesser extent, carbonyl cyanide 3-chlorophenylhydrazone in SHR atria compared with NWR atria. The higher responses in SHR rats suggest the existence of an augmented endoplasmic reticulum Ca(2+) store and faster mitochondrial Ca(2+) cycling in SHR atria compared with NWR atria. These data support the hypothesis that a dysfunction of purinergic neurotransmission and enhanced sympathetic activity are contributing factors in the pathogenesis of hypertension.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Juliano Quintella Dantas
authors.initials: JQ
authors.lastname: Rodrigues
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Edilson Dantas
authors.initials: ED
authors.lastname: da Silva
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Kleber
authors.initials: K
authors.lastname: de Magalhães Galvão
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Regiane
authors.initials: R
authors.lastname: Miranda-Ferreira
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Afonso
authors.initials: A
authors.lastname: Caricati-Neto
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Neide Hyppolito
authors.initials: NH
authors.lastname: Jurkiewicz
authors.affiliation: Instituto Teófilo Hernando, Universidad Autonoma de Madrid, Madrid, Spain.
authors.forename: Antônio G
authors.initials: AG
authors.lastname: Garcia
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006325:Heart Atria; D006973:Hypertension / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D012433:Ryanodine; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium; D014544:Uridine Triphosphate