Respuesta hipotensora al tratamiento agudo con péptido natriurético auricular: su relación con la expresión y la actividad de la óxido nítrico sintetasa cardíaca en ratas espontáneamente hipertensas

摘要

Background Atrial natriuretic peptide (ANP) and nitric oxide (NO) increase diuresis and natriuresis and reduce vascular tone. We have previously demonstrated that NO is involved in ANP hypotensive effect in normotensive rats. Objective To assess the effect of ANP on mean blood pressure (MBP) and on NO system in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY), and the role of the inducible isoform of nitric oxide synthase (iNOS). Material and Methods Protocol 1: animals were instilled with saline solution (0.05 ml/min) or with ANP (0.2 μg/kg/min) for an hour. MBP and urinary nitrites and nitrates (NOx) were assessed. The heart was extracted and iNOS and endothelial iNOS (eNOS) activity (with L-[U14C]-arginine) and expression (Western blot) were determined. Protocol 2: after adding ANP (1 μM), cANP(4-23) (NPR-C agonist, 1μM) or aminoguanidine (iNOS inhibitor, 1 μM) NOS activity in the right atrium and left ventricle of SHR and WKY was determined. Results Instillation with ANP reduced MBP and increased NOx in both groups. NOS activity was greater in SHR, and increased with the instillation of ANP. In SHR, greater eNOS and iNOS protein levels were observed, which were not modified by ANP. iNOS basal activity was greater in SHR. In the atrium, ANP interacts only with NPR-C in order to activate NOS, and NPR-A/B receptors would also take part in the ventricle. In this experimental model, the development and maintenance of hypertension could involve alterations in the interaction between both systems, ANP and NO.