Amiloride reduces stroke and renal injury in stroke-prone hypertensive rats

Sepehrdad, Reza; Oruene, Alafuro; Chander, Praveen N.; Stier, Charles T.

doi:10.1016/s0895-7061(01)01321-8

Cited by 13 publications

(15 citation statements)

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“…We felt that a pretreatment regimen was better suited to answer this question, since a cotreatment schedule might not allow for amiloride to block Na ϩ /H ϩ exchangers and/or Na ϩ channels before they are activated by HTS and/or by T/HS. We used amiloride at a dose of 10 mg/kg, since previous publications have reported that amiloride can effectively attenuate inflammatory (21) or ischemic (40) injury at this dose. We found that in our shock model, amiloride failed to prevent and even potentiated the protective effects of hypertonic saline, calling into question the possibility that Na ϩ /H ϩ exchangers and/or Na ϩ channels may mediate the protective effects of HTS during shock.…”

Section: Discussionmentioning

confidence: 99%

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone

Fujiyoshi

Deitch

Feketeova

et al. 2005

Critical Care Medicine

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Section: Discussionmentioning

confidence: 99%

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone

Fujiyoshi

Deitch

Feketeova

et al. 2005

Critical Care Medicine

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“…31,32 SR or eplerenone administration in these same experimental models largely prevents aldosterone detrimental effects. 31,33 Relative to amiloride, experimental studies have shown reductions in proteinuria and a regression of glomerular lesions in hypertensive rats 29 and improvements in podocyte lesions and glomerulosclerosis in the 5/6 nephrectomy rat model treated with this drug, probably mediated by an inhibition of urokinase receptor. 30 However, to our knowledge, no clinical studies have previously evaluated the effect of amiloride on patients with proteinuria.…”

Section: Kidney Internationalmentioning

confidence: 99%

“…27,28 There is no clinical information available on amiloride concerning its possible antialbuminuric effect, but experimental models have suggested a possible nephroprotective role of this diuretic. 29,30 To the best of our knowledge, there are no clinical studies that have compared the antialbuminuric efficacy of various types of diuretics. This information would be extremely important for the design of renoprotective clinical strategies, given that the use of various types of diuretics is standard practice for controlling BP and volume overload in CKD patients.…”

mentioning

confidence: 99%

Diverse diuretics regimens differentially enhance the antialbuminuric effect of renin–angiotensin blockers in patients with chronic kidney disease

Morales

Caro

Gutiérrez

et al. 2015

Kidney International

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The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochlorothiazide (50 mg/day) without/with amiloride (5 mg/day) on top of enalapril treatment in 21 patients with CKD stages 1-3 and a urinary albumin-to-creatinine ratio (UACR) over 300 mg/g. Treatment periods lasted 4 weeks. The UACR showed a significant reduction with the diuretics: spironolactone, -34% or hydrochlorothiazide without/with amiloride -42% or -56%, respectively. Reduction of the UACR was significantly greater with hydrochlorothiazide without/with amiloride when compared with spironolactone. The percentage of patients who achieved UACR reductions greater than 30% and 50% was greater with hydrochlorothiazide without/with amiloride (81% and 57%, and 81% and 66%, respectively) when compared with spironolactone alone (57% and 28%, respectively). Glomerular filtration rate (GFR), blood pressure, and body weight decreased with the three diuretic regimens. A significant correlation was found between the UACR reduction and GFR and blood pressure changes. Thus, diverse diuretic regimens differentially enhance albuminuria reduction, an effect likely associated with the degree of GFR reduction.

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“…Aldosterone has also been reported to induce the formation of proteins that stabilize and enhance the activity of sodium channels. Since the action of anti-aldosterone agents may also relate to interfering with these events, we examined whether amiloride, a potent and directly acting ENaC inhibitor, would mimic the anti stroke activity of MR antagonism in SHRSP [31]. We found that chronic treatment with amiloride at 1 mg/kg/day markedly increased the survival of SHRSP compared with untreated saline-drinking SHRSP littermate controls.…”

Section: Mr Antagonism In Stroke-prone Spontaneously Hypertensive Ratsmentioning

confidence: 99%

Effect of Aldosterone and MR Blockade on the Brain and the Kidney

2005

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The renin-angiotensin-aldosterone system (RAAS) plays a central role in the development of hypertension and the progression of end-organ damage. Although angiotensin-I converting enzyme (ACE) inhibitors and angiotensin II (Ang II) subtype-1 (AT(1)) receptor antagonists can initially suppress plasma aldosterone, it is now well established that aldosterone escape may occur whereby aldosterone levels return to, or exceed, baseline levels. The classical effects of aldosterone relate mainly to its action on epithelial cells to regulate water and electrolyte balance. However, the presence of mineralocorticoid receptors (MR) at nonepithelial sites in the brain, heart and vasculature, is consonant with the fact that aldosterone also has direct effects in these tissues. Substantial evidence now exists that supports the action of aldosterone at non-epithelial sites which in turn provokes a number of deleterious effects on the cardiovascular system including necrosis and fibrosis of the vasculature and the heart, vascular stiffening and injury, reduced fibrinolysis, endothelial dysfunction, catecholamine release and production of cardiac arrhythmias. Several studies have now shown that vascular and target-organ protective effects of MR antagonism occurs in the absence of significant blood pressure lowering or fluid loss, which is consistent with a major role for endogenous mineralocorticoids as direct mediators of cardiovascular injury. Adverse cardiovascular effects may occur in response to aldosterone alone, activation of the RAAS or aldosterone escape during chronic ACE inhibition or AT(1) receptor antagonism. The specific blockade of aldosterone action should prove to be of great therapeutic value in the prevention of cerebral and renal vascular disease and associated end-organ damage.

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Amiloride reduces stroke and renal injury in stroke-prone hypertensive rats

Cited by 13 publications

References 0 publications

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone

Diverse diuretics regimens differentially enhance the antialbuminuric effect of renin–angiotensin blockers in patients with chronic kidney disease

Effect of Aldosterone and MR Blockade on the Brain and the Kidney

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