Cardiovascular nitric oxide system activation via C-type natriuretic peptide: receptors and signaling pathways involved.

MARÍA ÁNGELES COSTA; ROSANA ELESGARAY; CAROLINA CANIFFI; SEBASTIÁN FINELLA; MARÍA FLORENCIA VISINTINI JAIME; ANA CAROLINA BURGER; ANDREA FELLET; ANA MARIA BALASZCZUK; CRISTINA ARRANZ

Milan, Italia

Congreso; Seventeenth European Meeting on Hypertension; 2007

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 (1µM), cANP (4-23) (a selective NPRC ligand, 1 µM), 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. 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. ±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.