IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cardiovascular nitric oxide system activation via C-type natriuretic peptide: receptors and signaling pathways involved
Autor/es:
COSTA MARIA DE LOS ANGELES; ELESGARAY ROSANA; CANIFFI CAROLINA; FINELLA SEBASTIÁN; VISINTINI JAIME MARIA FLORENCIA; BURGER CAROLINA; BALASZCZUK ANA MARÍA; ARRANZ CRISTINA
Lugar:
Milan Italia
Reunión:
Congreso; Seventeenth European Meeting on Hypertension.; 2007
Institución organizadora:
European Society of Hypertension
Resumen:
In previous studies we demonstrated that the diuretic and hypotensive effects of the atrial natriuretic peptid (ANP) involved the activation of nitric oxide synthase (NOS). Another member of the natriuretic peptide family is C-type natriuretic peptide (CNP) that is expressed in nervous system, vascular endothelium and heart, among others. CNP is less potent inducer of diuretic and natriuresis than ANP but is more potent in eliciting smooth muscle relaxation. Objective: The aim was to investigate changes in the mean arterial pressure (MAP, mmHg) and NO system induced by CNP and the receptor type and the possible mechanisms of signaling involved in this effects. Desing and methods: Nitrites and nitrates excretion (NOx, nmol/min.100g). NOS cathalytic activity (pmol/min.g tissue) was determined by measuring the convertion of L-[U14C]-Arginine to L-[U14C]-citrulline, after the addition of CNP (1ìM), cANP (4-23) (a selective NPR-C ligand, 1 ìM), Pertussis Toxin (PTx, Gi protein inhibitor, 800 ng/ml) in aorta artery, cardiac atria and ventricle from male Wistar rats. Results: MAP was diminished by CNP infusion (81±3 vs 95 ±4, p<0.01); CNP increase NOx (5.7 ±0.5 vs 1.6 ±0.2, p<0.01). NOS activity Basal CNP cANP TxP CNP+TxP CNP + cANP Aorta artery 217.3±4.4 266.8±1.3* 308.4±3.1*# 209.6±3.5 261.1±1.3* 366.1±3.8*#+ Right atria 233.6±3.6 284.1±1.1* 358.2±1.7*# 249.1±4.7 234.56±5.6# 356.3±3.2*# Left ventricle 175.3±2.8 230.1±3.8* 242.2±4.9* 170.1±3.0 225.3±5.6* 297.2±6.0*#+ *p<0.01 vs basal, # p<0.01 vs CNP, + p<0.01 vs cANP. CNP increase NOS activity in aorta, atria and ventricle, compared with basal activity. NOS activity induced by CNP were blunted by PTx addition in atria but Gi inhibition did not modified NOS activation via CNP in aorta and ventricle. Conclusions: These results suggests that the activation of NO system wuold be one of the mechanisms involved in cardiovascular effects of CNP. The peptide increase NOS activity in all studied tissues. In aorta and ventricle NPR-A and/or NPR-B receptor are involved in NOS activation via CNP. In atria, this activation would involved the interaction between CNP and NPR-C receptor associated to Gi protein.