Central NOS inhibition differentially affects vasopressin gene expression in hypothalamic nuclei in septic rats.
Our aim was to investigate the effect of central NOS inhibition on hypothalamic arginine vasopressin (AVP) gene expression, hormone release and on the cardiovascular response during experimental sepsis. Male Wistar rats were intracerebroventricularly injected with the non-selective NO synthase (NOS) inhibitor (L-NAME) or aminoguanidine, a selective inhibitor of the inducible isoform (iNOS). After 30 min, sepsis was induced by cecal ligation and puncture (CLP) causing an increase in heart rate (HR), as well as a reduction in median arterial pressure (MAP) and AVP expression ratio (AVP(R)), mainly in the supraoptic nucleus. AVP plasma levels (AVPp) increased in the early but not in the late phase of sepsis. L-NAME pretreatment increased MAP but did not change HR. It also resulted in an increase in AVPp at all time points, except 24h, when it returned to basal levels. AVP(R), however remained reduced in both nuclei. Aminoguanidine pretreatment resulted in increased MAP in the early phase and higher AVP(R) in the supraoptic, but not in the paraventricular nucleus, while AVPp remained elevated at all time points. We suggest that increased central NO production, mainly inducible NOS-derived, reduces AVP gene expression differentially in supraoptic and paraventricular nuclei, and that this may contribute to low AVP plasma levels and hypotension in the late phase of sepsis.
Oliveira-Pelegrin
Gabriela Ravanelli
GR
Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
de Azevedo
Sergio Vicente
SV
Yao
Song Tieng
ST
Murphy
David
D
Rocha
Maria José Alves
MJ
D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013495:Supraoptic Nucleus / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
D001127:Arginine Vasopressin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester