China
Africa
Explore chapters and articles related to this topic
Outpatient Management of Stable Heart Failure with Reduced Ejection Fraction
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Leah Reid, Jonathan Murrow, Kent Nilsson, Catherine Marti
Loop diuretics are the most potent of all diuretic agents. The four most used drugs in this class are furosemide, bumetanide, torsemide, and ethacrynic acid. Loop diuretics are protein-bound and not freely filtered by the glomerulus; they are secreted into the tubular lumen. Importantly, this secretion is impaired by and the action of these drugs limited by the concurrent presence of organic acids, which occurs in renal failure or in the presence of probenecid, salicylates, or nonsteroidal anti-inflammatory drugs.40 Once secreted into the tubule, loop diuretics compete with chloride molecules to bind to the Na+/K+/2Cl− cotransporter, thereby inhibiting reabsorption of sodium and chloride. Urinary diuretic concentration correlates with the natriuretic response following administration of a diuretic.41
Hormonal Regulation of Cholangiocyte Secretion
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Alessandro Gigliozzi, Flavia Fraioli, James L. Boyer
Like other chloride secreting epithelia, cholangiocytes also express a Na+,K+-2Cl− cotransporter on its basolateral membrane that functions to facilitate chloride uptake into the cell. This transporter thus helps to maintain high intracellular chloride concentrations that facilitate conductive chloride excretion into the biliary lumen upon opening of apical chloride channels. Subsequendy, the luminal Cl-/HCO3− exchanger is activated.24
Antihypertensive Drug Classes
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Engi Abdel-Hady Algharably, Reinhold Kreutz
Loop diuretics exert their effects at the thick ascending limb of the loop of Henle, where they inhibit Na+/K+/2Cl—cotransporter (NKCC). Loop diuretics are more potent diuretics than thiazides, but they are shorter acting, causing reflex stimulation of the RAS, which attenuates their BP-lowering efficacy (10). Because of their pharmacodynamics and kinetic profile, they have no place in the routine management of hypertension in patients with normal renal function. They should replace thiazides, however, if eGFR is >30 mL/min/1.73 m2 or their use is required to control volume status of patients; e.g. with severe oedema (2).
Antinociceptive activity of doliroside B
Published in Pharmaceutical Biology, 2023
Xishan Bai, Yanhong Li, Yuxiao Li, Min Li, Ming Luo, Kai Tian, Mengyuan Jiang, Yong Xiong, Ya Lu, Yukui Li, Haibo Yu, Xiangzhong Huang
Ion channels also play an important role in the occurrence of pain, DBDS exhibited antinociceptive activity which was possibly related to ion channels, whereupon we decided to investigate its possible antinociceptive mechanism on several ion channels, such as GABAA1, Nav1.7 and TRPV1 channels. GABAA receptors are widely expressed in brain and spinal cord pain circuits as the principal mediator of inhibitory neurotransmission. Several studies demonstrated that modulation of GABAA receptors showed great potentials for pain alleviation (Knabl et al. 2009; Bonin et al. 2011; Munro et al. 2013; Klinger et al. 2015). GABAA1 (α1β2γ2) is the most abundant isoform among GABA receptors. Therefore, the effect of DBDS on GABAA1 receptor was tested by using FMP-Blue-Dye method. For the FMP assay in the recombinant GABAA1 receptors expressed in T-REx™-CHO cells, as reported (Joesch et al. 2008), it was observed that exposure of agonist GABA resulted in depolarization of cells. In immature neurons, GABAA receptor agonists also depolarized the membrane potential, in contrast to hyperpolarizing in mature cells. These might be caused by intracellular Cl− accumulation due to the absence of Na-K-2Cl cotransporter (Plotkin et al. 1997). Therefore, GABA-induced depolarization in the recombinant cells might be the same as the immature neurons. Through ion channel assay, we found that compound DBDS might be allosterically modulating the function of GABAA1 receptor.
Emerging drug targets for sickle cell disease: shedding light on new knowledge and advances at the molecular level
Published in Expert Opinion on Therapeutic Targets, 2023
KCl cotransport inhibitors: The third potential target for specific transport pathway inhibitors is KCC. Like PIEZO1 and the Gárdos channel, KCC is found in red cells from normal individuals and also in other tissues, notably transporting epithelia [56]. KCC is also homologous to the Na+-linked cotransporter, NKCC, which is present in two isoforms, a housekeeping NKCC1 present in many tissues and a renal-specific NKCC2, the target of the loop diuretics. A major problem, again, therefore is one of specificity. Nevertheless, its significance as one of the three main dehydration pathways of sickle cells warrants attention. A number of bumetanide/furosemide analogues were synthesized by Hoechst in the 1980s [223]. One of these, H74, was shown to be effective in inhibiting KCC in human red cells, with good specificity over NKCC1 but no further developments have been reported. KCC is also notable in its regulation by protein phosphorylation [68–70], and the potential for this as a target is discussed in the next section.
The roles of hydrogen sulfide in renal physiology and disease states
Published in Renal Failure, 2022
Jianan Feng, Xiangxue Lu, Han Li, Shixiang Wang
H2S plays an important role in renal excretion. Xia et al. found that both CBS and CSE can produce H2S in the kidney and that when either enzyme is inhibited, the expression of the other increases to compensate. They also found that in anesthetized Sprague–Dawley rats, infusion of NaHS in the renal artery can increase renal blood flow and the glomerular filtration rate (GFR). Because of the increase in the filtration rate, those authors speculated that the role of H2S in vasodilating blood vessels was greater in preglomerular arterioles than in postglomerular arterioles. H2S can also inhibit the Na–K–2Cl cotransporter in the ascending limb of the loop of Henle and the Na–K ATPase enzyme, potentially increasing the excretion of sodium and potassium from urine. Therefore, H2S participates in both vascular and tubular actions in the kidneys [23].