Objectives: To test whether simply increasing plasma potassium with amiloride would exert any of the same beneficial effects on “surrogate outcome measures” that are seen with spironolactone. The latter has been shown to improve mortality in chronic heart failure, possibly as a result of improvements in endothelial dysfunction, vascular angiotensin converting enzyme (ACE), autonomic function, m...

Three structural classes of commonly used amiloride analogs, molecules derivatized at the terminal guanidino-nitrogen, the five-position pyrazinoyl-nitrogen, or di-substituted at both of these positions, inhibit binding of the L-type Ca2+ channel modulators diltiazem, gallopamil, and nitrendipine to porcine cardiac sarcolemmal membrane vesicles. The rank order of inhibitory potencies among the ...

Na+ transport across the lamprey erythrocyte membrane was examined using 22Na as a tracer. Both Na+ influx and Na+ effux exhibit a wide variability among different lampreys due to amiloride-sensitive components. Addition of 1 mmol/l amiloride to incubation media resulted in a decrease of the Na+ influx from 8.4 +/- 0.9 to 5.5 +/- 0.3 mmol/l cells/h (n = 18, P < 0.001), and of the rate coefficie...

The T594M polymorphism of the epithelial sodium channel is found in approximately 5% of people of African origin and is significantly associated with high blood pressure. Although the T594M polymorphism could increase renal sodium absorption through affected channels, it is not known whether this polymorphism causes hypertension. Amiloride specifically inhibits overactive sodium channels and ef...

The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In the present study, we used Ussing chamber experiments to investigate the effect of amiloride on the transmesothelial electrical resistance (R(TM)) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated directly after the death of the animals and were transferred t...

Previous studies in native T-type currents have suggested the existence of distinct isoforms with dissimilar pharmacology. Amiloride was the first organic blocker to selectively block the native T-type calcium channel, but the potency and mechanism of block of this drug on the three recombinant T-type calcium channels (Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3) have not been systematically determined. T...

Na(+)/H(+) exchanger (NHE) activation has been documented to contribute to endothelial cell injury caused by inflammatory states. However, the role of NHEs in regulation of the endothelial cell inflammatory response has not been investigated. The present study tested the hypothesis that NHEs contribute to endothelial cell inflammation induced by endotoxin or interleukin (IL)-1beta. NHE inhibiti...

The transduction of sodium salts occurs through a variety of mechanisms, including sodium influx through amiloride-sensitive sodium channels, anion-dependent sodium movement through intercellular junctions and unidentified amiloride-insensitive mechanisms. Characterizations of sodium transport in lingual epithelium mounted in Ussing chambers have focused almost exclusively on epithelia containi...

Pathophysiological features of both primary aldosteronism and pseudohyperaldosteronism are hyperactive amiloride-sensitive epithelial Na(+) channels (ENaC) and refractory hypertension. Peripheral blood lymphocytes express ENaC, which functions and is regulated similarly to ENaC expressed by renal principal cells. Thus it was hypothesized that individuals with either of these hypertensive etiolo...