1 A double-blind comparison of the effect of tienilic acid (250 mg) and amiloride (5 mg) on renal function in healthy volunteers and of tienilic acid plus amiloride compared to hydrochlorothiazide (50 mg) plus amiloride in patients with mild to moderate essential hypertension for safety and hypotensive efficacy was made.2 Renal plasma flow ([I125] iodohippurate clearance) and glomerular filtration rate ([1"31] iothalamate clearance and 24 h creatinine clearance) were not affected by tienilic acid or amiloride alone or in combination despite a rise in plasma urea and plasma creatinine (within the normal range) in healthy volunteers. 3 In hypertensive patients tienilic acid and tienilic acid plus amiloride treatments caused a rise in plasma urea and plasma creatinine similar to hydrochlorothiazide and hydrochlorothiazide plus amiloride but no significant change in creatinine clearance occurred with any of the treatments. 4 Tienilic acid and hydrochlorothiazide caused hypokalaemia in the patients which was normalized by addition of amiloride. Fewer subjects became hypokalaemic when amiloride was added to tienilic acid than when tienilic acid was given alone. 5 The antihypertensive effect of tienilic acid and tienilic acid plus amiloride was similar to hydrochlorothiazide and hydrochlorothiazide plus amiloride in patients with hypertension. No effect on blood pressure was observed in the healthy volunteers. 6 Plasma uric acid was significantly reduced by tienilic acid alone and in combination in patients and subjects whereas a significant elevation occurred with hydrochlorothiazide. 7 Side effects were increased when amiloride was added to either tienilic acid or hydrochlorothiazide, but side effects were less common after treatment with tienilic acid than following hydrochlorothiazide. 8 The combination of tienilic acid plus amiloride significantly reduces blood pressure and appears to be well tolerated with no adverse effects on renal function or plasma potassium in patients with mild to moderate hypertension and normal renal function. Addition of amiloride may be useful if hypokalaemia occurs following tienilic acid therapy in such patients.
Resting neutrophils may be “primed” to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N- dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(- 9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.
Prazosin was used as additional therapy in seven patients with severe chronic congestive cardiac failure. The effect on renal function in this situation was measured. Renal function improved in four of the seven patients, and this improvement was associated with improvement in their clinical condition; in two other patients, modest improvement in renal function was not associated with symptomatic relief which may have been the result of a gain in weight.
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