Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Author Lameu, Claudiana Google Scholar
Pontieri, Vera Google Scholar
Guerreiro, Juliano R. Google Scholar
Oliveira, Eduardo F. Autor UNIFESP Google Scholar
Silva, Carlos Alberto da Google Scholar
Giglio, Joyce M. Google Scholar
Melo, Robson L. Google Scholar
Campos, Ruy Ribeiro Autor UNIFESP Google Scholar
Martins de Camargo, Antonio Carlos Google Scholar
Ulrich, Henning Google Scholar
Institution Universidade de São Paulo (USP)
Inst Butantan
Universidade Federal de São Paulo (UNIFESP)
Univ Fed FABC
Abstract Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. the effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G(i/o)-protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010) 33, 1283-1288; doi: 10.1038/hr.2010.208
Keywords argininosuccinate synthase
baroreflex sensitivity
Bothrops jararaca venom
nitric oxide
proline-rich oligopeptide
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2010-12-01
Published in Hypertension Research. London: Nature Publishing Group, v. 33, n. 12, p. 1283-1288, 2010.
ISSN 0916-9636 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 1283-1288
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000285087000011

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