The Renin-Angiotensin System
Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan in Pharmacological and Therapeutic Aspects of Hypertension, 2020
Renin (EC 3.4.99.18) is a proteolytic enzyme with a mol wt of approximately 40,000 which occurs mainly in the kidney. It catalyzes the cleavage of angiotensin I from the amino terminus of a glycoprotein substrate. It is stored in the kidney in intracellular granules of the juxtaglomerular cells;11,12 these are modified myoepithelial cells present at the vascular pole of the glomerulus in the afferent and in efferent arterioles as well as the adjoining mesangium.13,14 Together with a specialized region of the distal tubule named the macula densa, the renin-containing cells form a morphological unit, the juxtaglomerular apparatus.15,16 Reninlike enzymes have been found in other organs as discussed below.
Medical evaluation and management of pregnant patients undergoing non-obstetrical surgery
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
The cardiovascular system undergoes significant alteration under the influence of the altered hormonal milieu of pregnancy. Progesterone inhibits distal tubular sodium reabsorption leading to natriuresis. The juxtaglomerular cells of the kidney in response to this secrete renin to stimulate aldosterone release from the adrenals, maintaining sodium homeostasis (1–3). Renin is converted into angiotensin and catecholamines are released from the adrenal gland. Pregnancy is a state of maternal hyper-catecholaminism from its early stages. These catecholamines stimulate both inotropic and chronotropic effects on the heart, leading to an increase in cardiac output. Cardiac output begins to rise in the first trimester and continues on a steady increase to peak at 30% to 50% of the preexisting levels by approximately 32 weeks of gestation (3–7). Both heart rate and stroke volume increase. Peripheral systemic vascular resistance is reduced secondary to progesterone, exerting a direct effect to relax the intimal smooth muscle in the precapillary resistance vessels (2,3). The resulting vasodilatation leads to a decreased vascular resistance. There is a slight decrease in mean arterial pressure in the second trimester of a normal pregnancy due to the reduction in peripheral resistance. Blood volume increases with pregnancy, peaking at approximately 50% of prepregnancy levels at around 32 weeks of gestation. As the pregnant woman approaches term, mean arterial pressure normalizes as the increase in blood volume compensates for the decreased resistance and fills the capacitance of the vasculature (8,9).
Shy-Drager Syndrome and Multiple System Atrophy
David Robertson, Italo Biaggioni in Disorders of the Autonomic Nervous System, 2019
Several peptide systems related to blood pressure control have also been studied in patients with autonomic failure. The renin-angiotensin system participates in the regulation of haemodynamics and electrolyte balance (for review see Skeggs, 1984). Reductions in blood volume, renal perfusion pressure and plasma sodium activate the cascade of enzymatic reactions that result in the formation and release of angiotensin II, the dominant hormone of this system. Renin, released from juxtaglomerular cells in the kidney, initiates the sequence by its actions on angiotensinogen. Autonomic nervous system activity affects the renal handling of sodium and water through α and β-adrenergic receptors. The former affect renal blood flow, while the latter modulate secretion of renin. Patients with autonomic failure exhibit excessive nocturnal salt and water excretion (Wilcox, Aminoff and Slater, 1977). Their low supine plasma renin levels fail to increase in response to salt restriction, postural change or isoproterenol (Wilcox et al., 1974; Bannister, Sever and Gross, 1977; Wilcox, Aminoff and Slater, 1977; Baser et al., 1991).
Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT1 receptors
Published in Stress, 2020
Gabriel T. do Vale, Drieli Leoni, Arthur H. Sousa, Natália A. Gonzaga, Daniela L. Uliana, Davi C. La Gata, Leonardo B. Resstel, Cláudia M. Padovan, Carlos R. Tirapelli
Our results are in line with previous findings showing that acute restraint stress increased both MAP and HR (Busnardo et al., 2010, 2013; Crestani et al., 2010; Dos Reis et al., 2014). Additionally, we found that blockade of AT1 receptors with losartan reduced acute restraint stress-induced MAP increase. This observation corroborates previous findings showing that angiotensin II plays a role in acute stress-induced cardiovascular changes (Busnardo et al., 2014; Erdos et al., 2010; Jezova et al., 2008; Kubo et al., 2001; Saiki et al., 1997). On the other hand, losartan did not prevent the increase in HR induced by acute restraint stress, suggesting that AT1 receptors do not play a role in such response. Moreover, our findings suggested that acute restraint stress activated the RAS. In fact, circulating levels of angiotensin II are described to be increased after acute stress (Gonzaga et al., 2015; Yang, Lu, Yu, & Raizada, 1996). The sympathetic nervous system modulates RAS activation. Renal juxtaglomerular cells are in contact with sympathetic nerve varicosities that express post-junctional β1-adrenergic receptors and activation of these receptors increases renin release with further activation of the RAS (Montezano & Touyz, 2014). Thus, activation of the RAS during acute restraint stress could be mediated by the sympathetic system, whose activity is increased in such condition (Dos Reis et al., 2014; Crestani, 2016).
Atorvastatin protects against contrast-induced acute kidney injury via upregulation of endogenous hydrogen sulfide
Published in Renal Failure, 2020
Lin Yan, Lin Jiaqiong, Guo Yue, Li Xiaoyong, Tan Xuexian, Long Ming, Li Yinglan, Liao Xinxue, Huang Zena
In kidney, H2S is produced through four pathways, while CSE and CBS are the two dominated enzymes for its generation [38]. In physiological conditions, H2S was found to inhibit sodium transporters on renal tubular cells, and thus regulate the excretory function of the kidney [39]. Likewise, it also influences the release of renin from juxtaglomerular cells and thereby modulates blood pressure [40]. What’s more, H2S modulates urine concentration by upregulating renal AQP-2 protein expression [41]. Liu et al. [42] recently showed that both CSE and CBS levels were severely decreased in a cisplatin-treated rats. Moreover, in renal ischemia/reperfusion models, supplement of H2S exerted protective effect likely through anti-inflammatory, anti-apoptotic, and anti-oxidative responses [43,44]. In our study, serum level of H2S, as well as renal expression of CSE and CBS, were significantly reduced in the CM-treated rats, paralleling to the renal injury. This indicated a decrease of systemic and localized generation of H2S in CIAKI model. Furthermore, when a H2S donor, NaHS, was employed in NRK-52E cells, CM-induced apoptosis and inflammation were both ameliorated remarkably. Therefore, our data prompted that H2S may also exhibited protection against CIAKI by anti-inflammatory, antiapoptotic, and antioxidative mechanism.
Advances in understanding the role of angiotensin-regulated proteins in kidney diseases
Published in Expert Review of Proteomics, 2019
Ana Belén Sanz, Adrian Mario Ramos, Maria Jose Soler, Maria Dolores Sanchez-Niño, Beatriz Fernandez-Fernandez, Maria Vanessa Perez-Gomez, Marta Ruiz Ortega, Gloria Alvarez-Llamas, Alberto Ortiz
Renin is secreted by kidney juxtaglomerular cells in response to sodium content in the tubular fluid. Renin enzymatic activity processes circulating angiotensinogen to angiotensin I, which in turn is converted to angiotensin II by the angiotensin-converting enzyme (ACE) (Figure 1). The RAS may be activated in the systemic circulation or within tissues. Angiotensin II binds to and activates the angiotensin II type 1 and type 2 receptors (AT1R and AT2R, respectively), among others. Through AT1R activation, angiotensin II promotes vasoconstriction, water intake, sodium retention, and increases oxidative stress, inflammation, fibrosis, and cell growth. This has been termed the classical RAS [6]. A key action is promoting secretion of the mineralocorticoid aldosterone by adrenal glomerulosa cells. Aldosterone activates the mineralocorticoid receptor and promotes sodium reabsorption and potassium secretion in distal tubules, in addition to other actions that promote tissue injury and fibrosis.
Related Knowledge Centers
- Afferent Arterioles
- Autoregulation
- Baroreceptor
- Efferent Arteriole
- Glomerulus
- Renin
- Smooth Muscle
- Kidney
- Cell
- Renin–Angiotensin System