C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats.
The aim was to study the effects of C-type natriuretic peptide (CNP) on mean arterial pressure (MAP) and the cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHR), and to investigate the signaling pathways involved in this interaction. SHR and WKY rats were infused with saline or CNP. MAP and nitrites and nitrates excretion (NO(x)) were determined. Catalytic NO synthase (NOS) activity and endothelial (eNOS), neuronal (nNOS) and inducible NOS (iNOS) were measured in the heart and aorta artery. NOS activity induced by CNP was determined in presence of: iNOS or nNOS inhibitors, NPR-A/B natriuretic peptide receptors blocker and Gi protein and calmodulin inhibitors. CNP diminished MAP and increased NO(x) in both groups. Cardiovascular NOS activity was higher in SHR than in WKY. CNP increased NOS activity, but this activation was lower in SHR. CNP had no effect on NOS isoforms expression. iNOS and nNOS inhibitors did not modify CNP-induced NOS activity. NPR-A/B blockade induced no changes in NOS stimulation via CNP in both tissues. Cardiovascular NOS response to CNP was reduced by Gi protein and calmodulin inhibitors in both groups. CNP interacts with NPR-C receptors, activating Ca-calmodulin eNOS via Gi protein. NOS response to CNP is impaired in the heart and aorta of SHR. Alterations in the interaction between CNP and NO would be involved in the maintenance of high blood pressure in this model of hypertension.
Caniffi
Carolina
C
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco, CONICET, Junín 956, Piso 7, 1113 Ciudad de Buenos Aires, Argentina.
Elesgaray
Rosana
R
Gironacci
Mariela
M
Arranz
Cristina
C
Costa
María Angeles
MA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase