Amiloride-sensitive Na+ pathways in capillary endothelial cell swelling during hemorrhagic shock

Mazzoni, Michelle C.; Intaglietta, Marcos; Cragoe, E. J.; Arfors, K. E.

doi:10.1152/jappl.1992.73.4.1467

Cited by 48 publications

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“…Endothelial cell swelling is a phenomenon observed in ischemia 21,22 and lactacidosis. 23 It is based on the activation of the plasma membrane Na ϩ /H ϩ exchanger inhibited by amiloride analogues as ethylisopropylamiloride.…”

Section: Discussionmentioning

confidence: 99%

Human Endothelium: Target for Aldosterone

et al. 2004

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Abstract-Aldosterone has long been known to control water and electrolyte balance by acting on mineralocorticoid receptors in kidney. However, recent studies demonstrated the presence of these receptors in nonclassical locations, including the cardiovascular system. We tested the hypothesis whether endothelial cells respond to aldosterone with changes in cell volume, a measure for ion-mediated water movement across the cell membrane. By means of atomic force microscopy in fluid, we measured volume of adherent human umbilical venous endothelial cells exposed for 72 hours to 10 nmol/L aldosterone. Over this period of time, cells swell by Ϸ18%. Aldosterone-induced swelling is prevented by 100 nmol/L of the mineralocorticoid receptor antagonist spironolactone, added to the primary endothelial cell culture. Aldosterone-treated cells dramatically shrink when 1 mol/L of the diuretic amiloride is applied. Cells deprived of aldosterone do not respond to amiloride. Our conclusions are: (1) aldosterone leads to sustained cell swelling inhibited by administration of spironolactone or the sodium channel blocker amiloride; (2) cells respond to amiloride after aldosterone exposure; (3) renal diuretics act on endothelial cells; and (4) Key Words: endothelium Ⅲ mineralocorticoids T he kidney is known to be the major target for aldosterone, a mineralocorticoid hormone synthesized in the adrenal cortex that acts on electrolyte transport in the distal nephron. 1 However, there is strong evidence that this hormone is also synthesized in heart 2 and blood vessels. 3 At these locations, it is regulated by similar mechanisms comparable to the renin-angiotensin aldosterone system. 4,5 Because of the fact that aldosterone acts on cardiomyocytes, cardiac fibroblasts, and endothelial cells, this hormone plays a major role in the development of heart failure, myocardial fibrosis, and endothelial dysfunction. 6 Moreover, there is much interest in the possibility of the use of aldosterone receptor blockade in patients to diminish pathological effects that can be produced by this hormone. 7 A study applying atomic force microscopy (AFM) on living aortic endothelial cells showed transient cell swelling that occurred over minutes and that was prevented by a high dose of amiloride known to inhibit plasma membrane Na ϩ /H ϩ exchange. 8 Although the underlying mechanism and its physiological relevance were still unclear, attention was placed on data suggesting that endothelial cells not only synthesize aldosterone 3 but also express mineralocorticoid receptors 9 and the epithelial sodium channel. 10 In a recent article, we applied cariporide, a specific Na ϩ /H ϩ exchange inhibitor, to human umbilical venous endothelial cells (HUVECs). 11 To our surprise, we found that the specific Na ϩ /H ϩ exchange inhibitor did not prevent aldosterone-induced cell swelling, whereas, in contrast, a low dose of amiloride known to block plasma membrane sodium channels was most effective. Taken together, these observations indicated that aldosterone triggers the "c...

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Section: Discussionmentioning

confidence: 99%

Human Endothelium: Target for Aldosterone

et al. 2004

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“…18,19 Capillary endothelial cell swelling, leukocyte-capillary plugging, and leukocytedependent edema after reperfusion lead to capillary noreflow. [20][21][22][23][24] In postcapillary venules, ROS promotes the production of chemotactic mediators and the expression of adhesion molecules on the surface of leukocytes and endothelial cells, contributing to endothelial barrier disruption and leukocyte adhesion. 25,26 These changes after reperfusion lead to microvascular damage.…”

Section: Discussionmentioning

confidence: 99%

Effect of Preinfarction Angina Pectoris on Myocardial Blush Grade After Reperfusion in First Anterior Wall Acute Myocardial Infarction

Tamura

Shinozaki

Watanabe

et al. 2006

Circ J

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he presence of preinfarction angina pectoris (PIA) has been shown to have beneficial effects on left ventricular (LV) function and prognosis after acute myocardial infarction (AMI). [1][2][3][4][5][6][7] Recently, myocardial blush grade (MBG) has been shown to be a simple and useful marker of myocardial tissue-level reperfusion in AMI. [8][9][10][11] Because the effect of PIA on MBG has not yet been investigated, we conducted the present study. Methods Study PatientsWe examined 142 consecutive patients (115 men, 27 women, mean age 61±11 years) with first anterior wall AMI who were admitted within 6 h after onset of symptoms and who met the following criteria: (1) typical chest pain lasting ≥20 min; (2) ST-segment elevation ≥0.2 mV in ≥2 adjacent precordial leads on the admission electrocardiogram; (3) an increase in the serum creatine kinase (CK) level more than twice the normal value; (4) no other heart or lung disease; (5) emergency coronary angiography and coronary angiography and left ventriculography performed at predischarge; and (6) adequate assessment of MBG after reperfusion. Informed consent for revascularization therapy and follow-up catheterization was given by all patients.PIA was defined as typical chest pain within 48 h before onset of AMI. Diabetes mellitus (DM) was considered present if this diagnosis and treatment, including diet, drugs, or insulin, had been given to the patient or if an abnormal oral glucose tolerance test or hemoglobinA1c ≥6.5% was found after admission. Cardiac CatheterizationEmergency coronary arteriography was performed using the Judkins or Amplatz technique. Multiple projections were recorded to ensure optimal visualization of the coronary vessels. The coronary flow in the infarct-related artery was graded according to the classification used in the Thrombolysis In Myocardial Infarction (TIMI) trial. 12 Proximal left anterior descending coronary artery (LAD) occlusion was defined as an occlusion of the artery proximal to its first septal branch. The grade of collateral filling in the LAD was determined according to the criteria of Rentrop et al. 13 A collateral circulation with a grade of 2 or 3 was defined as "good". After angiographic confirmation of total or subtotal occlusion of the LAD, primary coronary angioplasty was performed. If an optimal result (residual stenosis <50% without severe dissection) could not be obtained by balloon coronary angioplasty, coronary stenting was performed (n=59). Successful reperfusion was defined as the establishment of TIMI grade 3 flow in the infarct-related artery on the final coronary arteriogram. MBG was evaluated as follows 8 on the final left coronary angiogram in the lateral view after reperfusion: 0= no myocardial blush or contrast density; 1= minimal myocardial blush or contrast density; 2= moderate myocardial blush or contrast density, but less than that obtained during angiography of the con- Effect of Preinfarction Angina Pectoris on Myocardial Blush Grade After Reperfusion in First Anterior Wall Acute Myocardial Infarc...

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“…One was a standard hemorrhagic shock model in which the animal was acutely bled of 40% of its blood volume [2][3][4]. The procedure produced a protracted hypotension, metabolic acidosis, and global reduction in blood flow to nonessential organs such as skeletal muscle.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…Swelling of the endothelium with encroachment into the vessel lumen has been shown for capillaries in skeletal muscle [2][3][4] and mesentery [5] during hemorrhagic shock (global low-flow ischemia). The acute decrease in luminal diameter would increase hydraulic flow resistance, thereby hindering re flow efforts.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Implications of Capillary Endotheloal Swelling and Luminal Narrowing in Low-Flow Ischemias

et al. 1995

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Decreased functional capillary density (FCD) is a characteristic of low-flow ischemia which often persists on reperfusion of a tissue even though supply blood flow is reestablished. Capillary narrowing is a possible mechanism for the reduced blood reflow through an increase of the hydraulic resistance of the capillary network. We attribute the narrowing to swollen endothelial cells, a condition that could be observed directly and was found to develop with blood acidosis in both hemorrhagic shock and intentional acid infusion. A computer model of blood flow in skeletal muscle was used to predict the impact of a 21 % decrease in capillary luminal diameter on flow and leukocyte transit through the network. For hemorrhagic shock, reduction in blood flow due to capillary narrowing and lowered systemic pressure was offset by hemodilution causing a low-flow state. On reperfusion, flow could be restored if the narrowing was rectified by infusion of a hypertonic saline-dextran solution. Reinfusion with conventional Ringer’s lactate only partially restored flow because of a persistent capillary narrowing. The rheological contribution of passive leukocytes added only a few percent to network resistance even with shock-narrowed capillaries. With leukocyte activation increased cell cytoplasmic viscosity caused prolonged transit times for leukocytes in the network with a concomitant elevation in resistance. We conclude that capillary narrowing is a mechanism of FCD reduction in reperfusion after low-flow ischemia, either by a direct effect on flow or by enhancing the transient plugging of leukocytes. Therapeutic strategies should aim to ameliorate or prevent capillary endothelial cell swelling, and to minimize the level of activated circulating leukocytes.

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Amiloride-sensitive Na+ pathways in capillary endothelial cell swelling during hemorrhagic shock

Cited by 48 publications

References 0 publications

Human Endothelium: Target for Aldosterone

Human Endothelium: Target for Aldosterone

Effect of Preinfarction Angina Pectoris on Myocardial Blush Grade After Reperfusion in First Anterior Wall Acute Myocardial Infarction

Mechanisms and Implications of Capillary Endotheloal Swelling and Luminal Narrowing in Low-Flow Ischemias

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