C-type natriuretic peptide and cardiovascular nitric oxide system in hypertension.

COSTA MARIA DE LOS ANGELES; CANIFFI CAROLINA; RODRIGUEZ IERACE DANIELA; MARTORELL CARO MIGUEL ANGEL; ELESGARAY ROSANA; ARRANZ CRISTINA

Milán, Italia

Congreso; Nineteenth European Meeting of Hypertension; 2009

European Society of Hypertension.

C-type natriuretic peptide (CNP) plays an important role in cardiovascular homeostasis. In previous studies we demonstrated that CNP increases cardiovascular nitric oxide synthase (NOS) activity. The aim was to investigate changes in mean arterial pressure (MAP) and nitric oxide (NO) system induced by CNP and to elucidate natriuretic receptor and NOS isoform involved in the interaction between the peptide and NO-system in spontaneously hypertensive rats (SHR). Methods: A- In vivo studies: 12-weeks old SHR and normotensive Wistar Kyoto rats (WKY) were intravenously infused with saline (NaCl 0.9%) or CNP (1µg/Kg.min) during 60 minutes. MAP (mmHg) was recorded and nitrites and nitrates in plasma (PNOx, nM) and urine (UNOx, nmol/min.100g) were determined at the end of experimental time. Then animals were sacrifized by decapitation and NOS activity (using [14C] L-arginine as substrate) and endothelial NOS (eNOS) expression (Wsetern Blot) were determined in right atria (RA), left ventricle (LV) and aorta artery (AA). B- In vivo studies: NOS activity induced by CNP addition was determined in presence of: anatin (NPR-A/B receptors blocker), aminoguanidine (inducible NOS inhibitor) or 7-NI (neuronal NOS inhibitor) in heart and aorta of SHR. Results: A- In vivo: *p<0.01 vs WKY-saline; #p<0.01 vs SHR saline. Data between brackets correspond to difference between saline and CNP treatment for WKY or SHR CNP increased NOS activity in all tissues in both groups but the peptide did not modify eNOS expression. The stimulation of NO-system induced by CNP was accompanied to a decrease in MAP, but the response of this system to CNP was lower in SHR than in WKY. B- In vitro: NOS stimulation induced by CNP was not modified neither by NPR-A/B blockade nor by inducible or neuronal isoforms inhibition, indicating CNP interacts with NPR-C receptor activating eNOS. The impaired response of cardiovascular NO-system to cardiac antiproliferative actions attributed to CNP, the inadequate response of NO-system would be one of the mechanisms involved in the development of hypertrophy in this model of hypertension. MAP PNOx UNOx NOS activity RA NOS activity LV NOS activity AA WKY-saline 102±5 25.7±2.5 0.92±0.11 201.8±8.7 210.5±5.9 198.6±6.5 WKY-CNP 90±3 (12) 44.3±3.1* (18.6) 1.55±0.20* (0.63) 295.2±12.3* (93.4) 310.3±9.8* (99.8) 311.5±10.5* (112.9) SHR-saline 162±7* 38.4±2.9* 1.45±0.17* 329.8±15.4* 339.8±11.6* 348.1±13.2* SHR-CNP 136±8# (26) 50.2±5.8# (11.8) 1.85±0.23# (0.50) 398.4±19.6# (68.6) 425.2±17.3# (85.4) 429.4±20.1# (81.3)