Characterization of the L-arginine–NO–cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy

Abstract

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.

Effects of intravenous arginine on the healing of human skin graft donor sites: A randomized controlled trial

“…Arginine is the physiological precursor of NO, and it forms NO after catalyzed by NO synthase (Ognibene et al, 2010). Exogenous arginine is one of the ways to enhance the content of NO (Yurkiv et al, 2015).…”

Role of renin–angiotensin system and oxidative status on the maternal cardiovascular regulation in spontaneously hypertensive rats

“…The levels obtained from SHR-P were not significantly different from those of the normotensive groups, which is in agreement with previous findings. 15,17 These results might be partially explained by an increased production of NO and PGI 2 from vascular endothelium 25 and hyporeactivity to vasoconstrictors 5 which may contribute to vasodilation and consequent reduction in peripheral vascular resistance. It is widely accepted that an excess of NO is generated by endothelial cells during normal pregnancy.…”

PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis

“…Recently, it was demonstrated that inducible NOS (iNOS) or endothelial NOS (eNOS) are present neither in mouse nor in human platelets [ 36 ]. However, various works have shown the presence of eNOS/NO/sGC/cGMP signaling in platelets using by different experimental approaches including aggregation assays in presence of sGC and eNOS inhibitors [ 37 ], western blotting for eNOS [ 38 , 39 ], [ 3 H]L-citrulline [ 40 ] and cGMP production [ 37 , 38 ]. Therefore, in the present work we decided to investigate the role of sGC/cGMP/PKG pathway in the inhibitory effect of LPS-injection on platelet aggregation.…”