Ischemic stroke remains the fifth cause of death, as reported worldwide annually. Endothelial dysfunction (ED) manifesting with lower nitric oxide (NO) bioavailability leads to increased vascular tone, inflammation, and platelet activation and remains among the major contributors to cardiovascular diseases (CVD). Moreover, temporal fluctuations in the NO bioavailability during ischemic stroke point to its key role in the cerebral blood flow (CBF) regulation, and some data suggest that they may be responsible for the maintenance of CBF within the ischemic penumbra in order to reduce infarct size. Several years ago, the inhibitory role of the platelet NO production on a thrombus formation has been discovered, which initiated the era of extensive studies on the platelet-derived nitric oxide (PDNO) as a platelet negative feedback regulator. Very recently, Radziwon-Balicka et al. discovered two subpopulations of human platelets, based on the expression of the endothelial nitric oxide synthase (eNOS-positive or eNOS-negative platelets, respectively). The e-NOS-negative ones fail to produce NO, which attenuates their cyclic guanosine monophosphate (cGMP) signaling pathway and—as result—promotes adhesion and aggregation while the e-NOS-positive ones limit thrombus formation. Asymmetric dimethylarginine (ADMA), a competitive NOS inhibitor, is an independent cardiovascular risk factor, and its expression alongside with the enzymes responsible for its synthesis and degradation was recently shown also in platelets. Overproduction of ADMA in this compartment may increase platelet activation and cause endothelial damage, additionally to that induced by its plasma pool. All the recent discoveries of diverse eNOS expression in platelets and its role in regulation of thrombus formation together with studies on the NOS inhibitors have opened a new chapter in translational medicine investigating the onset of acute cardiovascular events of ischemic origin. This translative review briefly summarizes the role of platelets and NO biotransformation in the pathogenesis and clinical course of ischemic stroke.
Na nadciśnienie tętnicze choruje około 1/4 światowej populacji dorosłych. Ze względu na szerokie rozpowszechnienie, wpływ na śmiertelność i powodowane koszty socjoekonomiczne, ważne jest poszukiwanie modyfikowalnych przyczyn rozwoju tej choroby. W pracy tej został przeprowadzony przegląd piśmiennictwa w poszukiwaniu odpowiedzi na pytanie, czy w populacji dorosłych pacjentów (≥18r.ż) chorujących na nadciśnienie tętnicze częściej występuje zaburzenie lękowe z napadami lęku, niż w populacji ogólnej? W przeglądzie literatury znaleziono 10 badań przekrojowych opisujących związek pomiędzy nadciśnieniem tętniczym, a zespołem lęku panicznego. Iloraz szans współchorobowości tych dwóch jednostek chorobowych wynosił między OR = 3,31 (2,99-3,67), a AOR 1,19 (0,87–1,62). Natomiast częstość współwystępowania wahała się od 4,2%, do 18,75%. W badaniach prospektywnych wykazano zależność między zaburzeniem lękowym z napadami lęku, a następczym rozwinięciem się nadciśnienia tętniczego w ciągu życia jako OR= 1,7 (1,4–2,0). Z drugiej strony ryzyko rozwinięcia się zaburzenia lękowego z napadami lęku u badanych z nadciśnieniem tętniczym w czasie 12-miesięcznej obserwacji wynosiło OR= 3,23 (1,51–6,93), a z 3-letnim okresem obserwacji było nieistotne statystycznie OR= 1,12 (0,80–1,57). Na podstawie przeglądu literatury, ze względu na różnice w metodologii oraz małą ilość badań prospektywnych można jedynie sugerować klinicystom, by w niektórych przypadkach poszukiwali zaburzeń lękowych z napadami lęku u pacjentów z nadciśnieniem tętniczym, szczególnie przy obserwacji niekontrolowanych i krótkotrwałych wzrostów ciśnienia tętniczego.
Despite improvement in the management of modifiable cardiovascular risk factors, ischemic stroke remains the leading cause of morbidity and mortality in the adult population. The aim of this study was to analyze the time-dependent dynamic differences in expression of the nitric oxide (NO) metabolic pathway in the platelet and plasma compartment between subjects with and without ischemic stroke. Additionally, the interplay between these parameters and platelet aggregation was investigated. A total of 418 patients in acute phase of non-cardioembolic stroke were investigated. Following the inclusion and exclusion criteria, finally 40 subjects with stroke and 39 demographically matched healthy participants were enrolled. Neurological physical examination, followed by assessment of the platelet and plasma levels of the nitric oxide synthase (NOS) inhibitors, including asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as NOS substrate-L-Arginine were performed dynamically three times within the first 24-h, then on the 3rd and 7th day after the stroke onset, which was compared with the healthy control. The platelet L-Arginine concentration was significantly higher on the 1st and 3rd day of stroke, while the plasma levels were significantly lower on exact days in comparison to the control. The competitive NOS-inhibitors in platelets were stably elevated in stroke subjects, whereas no significant differences in plasma compartment were noted. The arachidonic-acid-induced platelet aggregation was negatively associated with the platelet NOS substrate bioavailability, as assessed by the L−Arginine ADMA-ratio on the 3rd and 7th day. Subjects with non-cardioembolic ischemic stroke are characterized by elevated platelet levels of NOS inhibitors. Management of stroke results in increasing the platelet L-Arginine concentration and subsequent NO bioavailability in the platelet compartment.
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