PaperAbstract Apelin (AP), an endogenous ligand of the APJ receptor, is involved in the regulation of cardiovascular homeostasis. Regardless the multiple similarities between AP and angiotensin II (Ang II), their roles seem to be different.We studied both the interactions between Apelin 13 (AP13) and Ang II and to what extent, if any, nitric oxide (NO) is involved.The experiments were performed in endothelium-denuded or endothelium-intact rat portal vein in the presence of 10 µM N(G)-nitro L-arginine methyl ester or 10 µM aminoguanidine.AP13 did not modify the isolated rat portal vein tone by itself, but inhibited the Ang II-induced contractions acting mainly by a NO-dependent mechanism. Our results sustain the hypothesis that AP13 could increase the activity of both constitutive and inducible NO synthase on either endothelium intact or endothelium denuded rat portal vein rings.
Accumulating evidence implicates nicotinic acid adenine dinucleotide phosphate (NAADP) in the control of Ca2؉ -dependent functions. Little, however, is known concerning its role in the vascular endothelium, a major regulator of blood pressure. Here, we show that NAADP acetoxymethyl ester (NAADP-AM), a cell-permeant NAADP analog, increases cytosolic Ca 2؉ concentration in aortic endothelial cells. We demonstrate that these signals and those evoked by acetylcholine are blocked by disrupting acidic organelles with bafilomycin A1. In contrast, Ca 2؉ signals in response to thrombin are only partially inhibited by bafilomycin A1 treatment, and those to ATP were insensitive, suggesting that recruitment of acidic stores is agonist-specific. We further show that NAADP-evoked Ca 2؉ signals hyperpolarize endothelial cells and generate NO. Additionally, we demonstrate that NAADP dilates aortic rings in an endothelium-and NO-dependent manner. Finally, we show that intravenous administration of NAADP-AM into anesthetized rats decreases mean arterial pressure. Our data extend the actions of NAADP to the endothelium both in vitro and in vivo, pointing to a previously unrecognized role for this messenger in controlling blood pressure.Nicotinic acid adenine dinucleotide phosphate (NAADP) 4 is a potent and widespread Ca 2ϩ -mobilizing messenger first described in sea urchin eggs (1, 2). Although its mechanism of action is subject to debate, much evidence indicates that NAADP mobilizes Ca 2ϩ from acidic, lysosome-like organelles (3) through activation of novel Ca 2ϩ -permeable channels (1, 4). These channels have recently been identified as members of the two-pore channel family (5-9). Importantly, mobilization of so-called "acidic Ca 2ϩ stores" (10) by NAADP is often linked to mobilization of the well established endoplasmic reticulum Ca 2ϩ stores through the process of Ca 2ϩ -induced Ca 2ϩ release (11). NAADP is thus thought to act as trigger during agonistevoked Ca 2ϩ signaling (2). The functional positioning of NAADP-sensitive Ca 2ϩ stores upstream of those targeted by the messengers, inositol 1,4,5-trisphosphate (IP 3 ) and cyclic ADP-ribose, raises the possibility that agonist-evoked Ca 2ϩ signals previously ascribed to endoplasmic reticulum Ca 2ϩ release might also involve NAADP and acidic organelles.Using isolated cells or tissues, NAADP-induced Ca 2ϩ signaling has been implicated in the regulation of several physiological functions such as egg fertilization (12, 13), T lymphocyte activation (14), muscle contraction (15), and neuronal differentiation (16). The role of NAADP in vivo, however is not known, although a recent study demonstrated that a newly described NAADP antagonist could prevent T cell motility in an animal model of multiple sclerosis (17).In the cardiovascular system, a role for NAADP has been demonstrated in agonist-evoked Ca 2ϩ signaling in pulmonary (15, 18) and coronary arteries (19,20), cardiac myocytes (21), and the renal microcirculation (22). Direct measurements of NAADP have confirmed its messenge...
Angiotensin (1-7) [Ang (1-7)] is a bioactive component of the renin angiotensin system. Ang (1-7) may interact with angiotensin type 1 (AT1) or type 2 (AT2) receptors and with Ang (1-7) — specific receptors. We examined the interactions between different doses of Ang (1-7) (1nM-1microM) and angiotensin II (Ang II) (10 and 100nM) on isolated rat portal vein. In endothelium-denuded portal vein rings, Ang (1-7) inhibited contractile effects induced by Ang II. The effects of Ang (1-7) were modified by indomethacin, N(G)-nitro-L-arginine methyl ester (L-NAME), (D-Ala7)-Angiotensin (1-7) (H-2888) and losartan. Our results suggest that on rat isolated portal vein rings without endothelium, Ang (1-7) reduces Ang II—induced contractions by acting mostly on Ang (1-7) specific receptors, and this effect is mediated by vasodilatatory prostaglandins. At high concentrations, Ang (1-7) effects are mediated by AT1-receptors, though to a lesser extent than by Ang (1-7) specific receptors.
The general perception is that the COVID-19 pandemic has been one of the biggest challenges for the health system. While touching every aspect of life, the COVID-19 pandemic has requested a prompt response from the health system and other structures and coordination systems that intervene in daily activity. The data presented were obtained following the application of a questionnaire to the average care staff of the Pascani Municipal Emergency Hospital, which monitored the impact of the COVID-19 pandemic on their professional activity and emotional state. The results revealed not only feelings of panic, fear, and worry but also determination and stubbornness in the fight against the disease. The results of the study indicated the adherence of the medical staff to initiatives that promote a holistic approach to the patient, addressing all the patient’s sufferings (physical, psychological, social, or spiritual), as well as finding new ways of relieving, treating, and healing them. The therapeutic act was difficult to fulfill because it had to consider the COVID-19 protocols, modified in dynamics, and applied to patients and staff. The use of complete protective equipment, as well as other adjustments to the working conditions, were perceived as an additional effort. To achieve this desideratum, teamwork, continuous medical education of the medical staff, and efficient communication between the medical assistant-nurse team with the patient and their relatives were of particular importance. Clear, transparent communication on the patient’s actual clinical condition and prognosis to his family members is essential to avoid and overcome possible conflictual situations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.