title: Mechanisms underlying the hypotensive and vasodilator effects of Ru(terpy)(bdq)NO](3+), a nitric oxide donor, differ between normotensive and spontaneously hypertensive rats.
abstract: The endothelium impairs the vasodilator effect of Ru(terpy)(bdq)NO](3+) (TERPY) in Wistar rat aortas. We hypothesized that endothelial dysfunction could modulate TERPY׳s effect in spontaneously hypertensive rats. The present study investigated the role of the endothelium in the hypotensive and vasodilator effects of TERPY in spontaneously hypertensive rats. We observed a higher hypotensive effect of TERPY in spontaneously hypertensive than in Wistar rats. l-N(G)-Nitroarginine methyl ester, a nitric oxide synthase inhibitor, increased TERPY׳s hypotensive effect in Wistar but not in spontaneously hypertensive rats. TERPY induced a concentration-dependent vasodilator effect in aortas of both rat models. Endothelium removal or l-NAME increased TERPY׳s potency in Wistar rat aortas; this effect was decreased in spontaneously hypertensive rats. TERPY increased nitric oxide level in spontaneously hypertensive rat endothelial cells; this increase was abolished in the presence of l-NAME. In contrast, this effect was increased in Wistar rats. TERPY, with or without l-NAME, decreased levels of reactive oxygen species in spontaneously hypertensive rat endothelial cells. However, it increased these levels in Wistar rats. TERPY reduced aortic endothelial nitric oxide synthase expression in Wistar rats, but did not alter its expression in spontaneously hypertensive rats. In conclusion, different mechanisms underlie the hypotensive and vasodilator effects of TERPY in these two rat models. TERPY reduced endothelial nitric oxide synthase expression and increased reactive oxygen species production in Wistar rat aortas, but did not alter these in spontaneously hypertensive rats. Furthermore, the nitric oxide released by TERPY reacts with reactive oxygen species, decreasing their bioavailability in spontaneously hypertensive rats.
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Simone R
authors.initials: SR
authors.lastname: Potje
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Munhoz
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Perassa
authors.affiliation: Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Murilo E
authors.initials: ME
authors.lastname: Graton
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Ariana A F
authors.initials: AA
authors.lastname: Pereira
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Ana Claúdia M S
authors.initials: AC
authors.lastname: Nakamune
authors.affiliation: Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP - University of São Paulo, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: da Silva
authors.affiliation: Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP - University of São Paulo, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil.
authors.forename: Doris H
authors.initials: DH
authors.lastname: Sumida
authors.affiliation: Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas - UNESP - Univ Estadual Paulista, Campus Araçatuba, São Paulo, Brazil; Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP - Univ Estadual Paulista, Araçatuba, SP 16015-050, Brazil. Electronic address: crisant@foa.unesp.br.
authors.forename: Cristina
authors.initials: C
authors.lastname: Antoniali
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012428:Ruthenium / Q000494:pharmacology / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D012428:Ruthenium
keywords: Endothelium; Hypotensive effect; Nitric oxide donor; Spontaneously hypertensive rats; Vasodilator effect