Salt-sensitive hipertensión in ß-endorphin knockout mice.

CAEIRO, X. ; GARCÍA, N. ; MARCELO RUBINSTEIN ; VIVAS L.

Aguas de Lindoia, San Pablo, Brasil

Congreso; XX Reunión Anual de la Fed. de Sociedades de Biología Experimental (FESBE).; 2005

Fed. de Sociedades de Biología Experimental

11.076 SALT-SENSITIVE HYPERTENSION IN ß-ENDORPHIN KNOCKOUT MICE 1Caeiro, X.; 2García, N.; 3Rubinstein, M.; 1Vivas L.; 1Instituto de Investigación Médica M.y M.Ferreyra; 2Renal Physiology, Instituto Privado de Especialidades Médicas S. A.; 3 Fisiologia INGEBI Universidad de Buenos Aires Objetivo: Several lines of evidence suggest that endogenous opioids participate in blood pressure (BP) regulation in normal conditions and that alterations in opioid system might contribute to the pathogenesis of hypertension. Central or systemic administration of ß-Endorphin (ß-End) decreases arterial BP and alterations in brain opioid peptides as well as in their receptors have been observed in both experimental and genetic hypertension. The stimulation of neurons in the arcuate nucleus (major source of ß-End) leads to the release of ß-End from nerve terminals in the nucleus of the solitary tract (NTS), where it acts and induces hypotension. Considering that lower levels of ß- Endorphins have been reported in both, experimental models of hypertension as well as in patients with essential hypertension, the objective of this study was to test the hypothesis that ß-End deficiency is involved in the development of salt sensitivity hypertension. Métodos e Resultados: Adult male mice of the three genotypes, Knockout (KO), Heterozygous (HT) and Wild type (WT) for ß-End, were maintained for a week on low sodium diet –LSD- (0.08%) and then were divided in two groups. The first one was maintained in same experimental conditions as mentioned above and in the second group, the LSD was changed for a high sodium diet –HSD- (4 %) for the following 2 weeks. The BP was significantly increased in ß-End KO mice compared with HT and WT groups (KO=17.3± 3.2 mmHg vs HT=7.28±3.4 mmHg, and WT=0.84±3.17 mmHg, p<0.05, n=8-10) after they had been fed during 2 weeks with HSD. This difference in BP between ß-End KO and HT and WT mice was not detected when these mice were fed with LSD. The experiments also indicate that ß-End KO mice fed during 2 weeks with a HSD, have an increased number of Fos immunoreactive neurons in the medial NTS when compared to WT animals (KO=71.33±6.0 vs WT=27.0±2.4, p<0.05, n=4). Conclusões: These results support the hypothesis that changes of endogenous opioids may be involved in salt sensitive hypertension and that the NTS might be one of the areas involved in the ß-End regulation of blood pressure.