Characterization of the L-arginine-NO-cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy.
Nitric oxide (NO) is a short-lived intercellular messenger that provides an efficient vascular regulatory mechanism to support homeostasis and prevent thrombosis. Endothelial dysfunction and reduced NO bioavailability have a central role in hypertension associated with pregnancy. The purpose of this study was to investigate the impact of pregnancy on the L-arginine-NO-cGMP pathway in platelets and its correlation to platelet function and blood pressure in normotensive rats and spontaneously hypertensive rats (SHRs). Platelets were obtained from blood on the 20th day of pregnancy from female SHRs (SHR-P) and normotensive controls (P) or age-matched nonpregnant rats (SHR-NP and NP). Intraplatelet NO synthase (NOS) activity was reduced in P compared to NP, despite unchanged L-arginine influx. The expression levels of endothelial NOS (eNOS) and inducible NOS (iNOS) were diminished during pregnancy in normotensive rats. Paradoxically, cyclic guanosine monophosphate (cGMP) levels were similar between NP and P, as were phosphodiesterase type 5 (PDE5) expression and platelet aggregation induced by adenosine diphosphate. In SHRs, L-arginine influx was reduced in SHR-P compared to SHR-NP. SHR-P exhibited impaired NOS activity and reduced iNOS expression compared with SHR-NP. Soluble guanylyl cyclase and PDE5 expression in platelets were lower in SHR-P than in SHR-NP, whereas no differences were noted between groups with respect to cGMP levels. However, increased levels of cGMP were observed in SHR-P compared to normotensive groups and platelet aggregability remained unaltered. In conclusion, these observations prompted the hypothesis that normal platelet aggregation in pregnant SHRs may be related to a reduction in PDE5 expression and consequently the maintenance of cGMP levels, independently of reduced platelet NO bioavailability.
Ognibene
Dayane Teixeira
DT
Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Moss
Monique Bandeira
MB
Matsuura
Cristiane
C
Brunini
Tatiana M
TM
de Moura
Roberto Soares
RS
Mendes-Ribeiro
Antônio Cláudio
AC
Resende
Angela de Castro
AC
D000818:Animals; D001120:Arginine / Q000378:metabolism* / Q000502:physiology; D001792:Blood Platelets / Q000201:enzymology; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000032:analysis; D005260:Female; D006162:Guanylate Cyclase / Q000032:analysis; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D010974:Platelet Aggregation; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006162:Guanylate Cyclase; D006152:Cyclic GMP