Functions of the Cardiovascular System
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The cardiovascular system can be considered to have as many roles as the diverse tissues and organs it supplies. The transfer of oxygen and carbon dioxide between the lungs and the tissues is the system's prime function. The gastrointestinal vessels absorb nutrients from the gut and perfuse the liver. The cardiovascular system then delivers these nutrients (glucose, amino acids and fatty acids) to the tissues for cellular metabolism and removes waste products. The renal circulation is essential for water and electrolyte homeostasis and the excretion of waste products. The cardiovascular system also has an important role in the distribution of body water between intravascular, extracellular and intracellular spaces: a reduction in the hydrostatic pressure in systemic capillaries facilitates the movement of interstitial and intracellular water into the intravascular space. The hormonal roles of the cardiovascular system include the delivery of endocrine hormones from their release sites to the target tissues and the production of atrial natriuretic peptide (ANP) within the heart. The cardiovascular system has an immune role, transporting antibodies and immune cells around the body. The cardiovascular system is involved in temperature regulation, as skin blood flow and thus heat loss can be varied according to body temperature.
Cardiovascular physiology
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
The cardiovascular system can be considered to have as many roles as the diverse tissues and organs it supplies. The transfer of oxygen and carbon dioxide between the lungs and the tissues is the system’s prime function. The gastrointestinal vessels absorb nutrients from the gut and perfuse the liver. The cardiovascular system then delivers these nutrients (glucose, amino acids and fatty acids) to the tissues for cellular metabolism and removes waste products. The renal circulation is essential for water and electrolyte homeostasis and the excretion of waste products. The cardiovascular system also has an important role in the distribution of body water between intravascular, extracellular and intracellular spaces: a reduction in the hydrostatic pressure in systemic capillaries facilitates the movement of interstitial and intracellular water into the intravascular space. The hormonal roles of the cardiovascular system include the delivery of endocrine hormones from their release sites to the target tissues and the production of atrial natriuretic factor (ANF) within the heart. The cardiovascular system has an immune role, transporting antibodies and immune cells around the body. The cardiovascular system is involved in temperature regulation, as skin blood flow and thus heat loss can be varied according to body temperature.
Role of Metabolism in Chemically Induced Nephrotoxicity
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Those conjugates that undergo glomerular filtration are either excreted in the urine (generally the mercapturates) or are reabsorbed into renal proximal tubular cells by active, sodium-dependent transport across the brush border membrane (Schaeffer and Stevens, 1987). Because only 30% of plasma is filtered through the glomerulus during a single pass through the renal circulation, a significant portion of chemicals cleared by the kidneys are taken up by processes localized to the basal-lateral membrane (Lash et al., 1988). Transport processes have been identified for several conjugates and their metabolites on the basal-lateral membrane in various in vitro systems, including renal cortical slices, membrane vesicles, isolated perfused kidney, isolated proximal tubules, and isolated proximal tubular cells (Boogaard et al., 1989; Inoue et al., 1981, 1984; Lash and Jones, 1983, 1984, 1985; Lash and Anders, 1989; Lock and Ishmael, 1985; Lock et al., 1986; Ulrich et al., 1989; Wolfgang et al., 1989; Zhang and Stevens, 1989).
The current and future status of inotropes in heart failure management
Published in Expert Review of Cardiovascular Therapy, 2023
Angelos Arfaras-Melainis, Ioannis Ventoulis, Effie Polyzogopoulou, Antonios Boultadakis, John Parissis
Dopamine is an endogenous molecule that can activate dopaminergic type 1 and 2, beta-1, and alpha-1 adrenergic receptors. When used at doses up to 2.5 µg/kg/min, it induces renal vasodilation by binding to the postsynaptic type 1 dopaminergic receptors, as well as splanchnic vasodilation by binding to the presynaptic type 2 dopaminergic receptors [8,39]. This effect leads to an increase in renal circulation, irrespective of cardiac output increases [40]. However, the clinical significance of the renal effects conferred by low-dose dopamine is disputed. For example, in the DAD-HF-II (Dopamine in Acute Decompensated Heart Failure II) study, the addition of low-dose dopamine to low-dose intravenous furosemide did not show any improvement in renal function, mortality or HF outcomes, when compared to the single low-dose furosemide treatment arm [21]. Additionally, the ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial also failed to demonstrate any significant improvement in 72-hour urine volume or decongestion markers in patients who received dopamine [22]. When used at moderate doses (3–5 µg/kg/min), dopamine primarily enhances cardiac contractility and chronotropy by acting on the cardiac beta-1 receptors. When used at high doses (>5 µg/kg/min), it leads to a net vasoconstrictive effect by stimulating alpha-1 receptors. It is worth mentioning that tachyarrhythmias occur with the use of dopamine especially at higher doses closer to 10 µg/kg/min or above, as well as in the setting of underlying hypertension [8,41,42].
Pharmacological management of portal hypertension and its complications in children: lessons from adults and opportunities for the future
Published in Expert Opinion on Pharmacotherapy, 2021
Sarah Henkel, Carol Vetterly, Robert Squires, Patrick McKiernan, James Squires
Hepatorenal syndrome (HRS) is a form of kidney function impairment that can occur in patients with cirrhosis. Two principle types have been identified: acute kidney injury (AKI)-HRS and chronic kidney disease (CKD)-HRS [57,87].. In adults, AKI-HRS portends a particularly poor prognosis with a median survival of < 3 months. Mechanistically, AKI-HRS is characterized by severe vasoconstriction of the renal circulation in the setting of inappropriately hyperdynamic cardiac physiology that occurs in cirrhosis in otherwise histologically normal appearing kidneys [87,88]. As is in adults, diagnosis of AKI-HRS in children is often complicated by the many alternative etiologies of renal injury in those with PHT. Treatment includes reversing precipitating factors, such as infections and gastrointestinal bleeding, volume expansion, paracentesis, and certain vasoconstrictors (i.e. terlipressin) [89] (Table 3). Notably in children, controversy persists relating to HRS and its management mainly attributed to difference in etiopathogenesis that is thought to drive disease [90].
Recent advances in drug discovery for diabetic kidney disease
Published in Expert Opinion on Drug Discovery, 2021
Chhanda Charan Danta, Andrew N. Boa, Sunil Bhandari, Thozhukat Sathyapalan, Shang-Zhong Xu
It can be concluded that RAAS inhibitors and SGLT-2 inhibitors are beneficial for DKD patients, but are not able to stop DKD progression completely. SGLT-2 inhibitors possess both antioxidative and anti-inflammatory properties, which could be beneficial in terms of pathogenesis of DKD, and further SGLT-2 inhibitors need to be developed. Additionally, SGLT-2 inhibitors such as canagliflozin, dapagliflozin, and empagliflozin have shown potential effects at multiple molecular targets or contributors of DKD. Therefore, it is a good indication for the discovery and development of better future therapeutics for the treatment of DKD considering these SGLT-2 inhibitors as standard in experimental models. Furthermore, potential SGLT-2 inhibitors can be designed and synthesized for biological testing. Some new therapeutic targets such as DPP-4, PKC, JAK, endothelin receptor, ORAIs/TRPCs, etc are involved in the pathological progression of DKD, and the development of inhibitors of these targets needs more investigation to validate their efficacy and safety before clinical applications. Furthermore, targeting renal circulation could be an alternative approach for DKD. For example, a combination of sacubitril and valsartan is under clinical trial phase III for DKD [1], Cinaciguat, a soluble guanylate cyclase (sGC) activator has shown promising preclinical results, and rosiglitazone, a PPARγ activator has been shown to reduce both microalbuminuria and blood pressure in T2DM patients independently of glycemia[130]. Long-term use of epalrestat, an aldose reductase inhibitor, on T2DM patients has shown some potential usefulness on renal functions [131]. Overall, there remains an urgent need for identification and validation of new drug targets and candidates to achieve better treatment of DKD.
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