Effects of MK-870 in Normal Subjects and Hypertensive Patients

Gombos, Ervin A.; Freis, Edward D.; Moghadam, Abdol Karim Zamani

doi:10.1056/nejm196612012752202

Cited by 59 publications

(17 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results compare with those of Gombos et al (1966), who studied the effects of amiloride and hydrochlorothiazide in 10 hypertensives who were already on other antihypertensive drugs. They found no significant difference between the hypotensive effect of amiloride, hydrochlorothiazide, or the two drugs in combination.…”

Section: Methodssupporting

confidence: 52%

“…med.J., 1968, 1, 422-423 In man amiloride hydrochloride has been shown to be an orally effective diuretic which causes a positive potassium balance. It also enhances the saluretic effects of hydrochlorothiazide and ethacrynic acid and in addition prevents the negative potassium balance caused by these diuretics (Wilson et al, 1966;Gombos et al, 1966). Gombos et al also studied its effects in 10 hypertensive patients, all of whom were on other antihypertensive agents.…”

Section: Amiloride Hydrochloride In Hypertensive Patientsmentioning

confidence: 99%

“…It also enhances the saluretic effects of hydrochlorothiazide and ethacrynic acid and in addition prevents the negative potassium balance caused by these diuretics (Wilson et al, 1966;Gombos et al, 1966 Control readings are the average for all cases for the second outpatient visit. Treatment averages include the three-and six-week readings for all patients.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Amiloride hydrochloride in hypertensive patients.

Paterson¹,

Dollery²,

Haslam³

1968

BMJ

View full text Add to dashboard Cite

In man amiloride hydrochloride has been shown to be an orally effective diuretic which causes a positive potassium balance. It also enhances the saluretic effects of hydrochlorothiazide and ethacrynic acid and in addition prevents the negative potassium balance caused by these diuretics (Wilson et al., 1966;Gombos et al., 1966 Control readings are the average for all cases for the second outpatient visit. Treatment averages include the three-and six-week readings for all patients.There was no significant difference between the average blood urea in the pretreatment period (31 mg./100 ml.) and the average blood urea when either amiloride alone (32 mg./100 ml.) or hydrochlorothiazide (33 mg./100 ml.) was given. However, on the combined diuretic regimen the average blood urea rose significantly to 40 mg./100 ml. as compared with the pretreatment value (P=0.013). The average plasma potassium was signicantly higher (P= 0.011) on amiloride (4.6 mEq/l.) than before treatment (4.2 mEq/l.). However, no individual value was higher than the upper limit of the normal range, and the highest value recorded was 5.1 mEq/l. On hydrochlorothiazide the average plasma potassium fell to 3.7 mEq/l., which was significantly less than control (P=0.016), and in addition three individual values were below the lower limit of normal (3.0, 3.1, 3.1 mEq/l.). On the combined regimen the average value (4.0 mEq/l.) was not significantly different from that before treatment; only one reading was below normal (3.7 mEq/l.) and the highest value was 4.3 mEq/1.

show abstract

Section: Methodssupporting

confidence: 52%

Section: Amiloride Hydrochloride In Hypertensive Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Amiloride hydrochloride in hypertensive patients.

Paterson¹,

Dollery²,

Haslam³

1968

BMJ

View full text Add to dashboard Cite

show abstract

“…For example, amiloride lowered the BP in severely hypertensive blacks, but at a dose of 20 mg per day. 10 . Spironolactone was shown to lower BP in low-renin hypertensive patients, 18 -21 but at much higher doses (100 to 400 mg/d).…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure Responses to Small Doses of Amiloride and Spironolactone in Normotensive Subjects

et al. 2001

View full text Add to dashboard Cite

Abstract-The epithelial sodium channel (ENaC) is a principal site for sodium reabsorption and as such may participate importantly in blood pressure (BP) regulation. Amiloride, a direct inhibitor of ENaC, characteristically has mild antihypertensive properties, consistent with ENaC having more minor influences on BP regulation. Counter-regulatory influences may, however, prevent amiloride from effectively lowering BP. Aldosterone secretion is known to increase in response to the reduced sodium reabsorption that follows amiloride inhibition of ENaC, and because aldosterone upregulates ENaC function, we considered the possibility that secondary hyperaldosteronism mitigates the ability of amiloride to reduce BP. In the present study, the BP responses to amiloride (5 mg per day), spironolactone (25 mg per day), the combination of the 2 drugs, and placebo were studied in healthy normotensive subjects. Over 4 weeks of treatment, the combination of amiloride and spironolactone lowered systolic BP by 4.6Ϯ1.6 (meanϮSEM) mm Hg (Pϭ0.022) and diastolic BP by 2.2Ϯ1.2 mm Hg (Pϭ0.30), whereas either drug alone had no significant effect on BP.The findings suggest that the 2 drugs with different modes of action-amiloride, a direct inhibitor of ENaC, and spironolactone, a mineralocorticoid receptor antagonist-may compliment each other's ability to inhibit ENaC and thereby reduce sodium reabsorption to a point at which BP decreases. On the other hand, we cannot rule out that the BP response resulted from the greater dose of total drug. 4 -6 or the life-threatening decrease in blood pressure (BP) that occurs in the neonatal period known as pseudohypoaldosteronism type 1. 7 More minor but common molecular variations in ENaC may also affect risk for hypertension. 8,9 If, indeed, ENaC is important for maintaining BP or contributing to the high BP of some individuals, then giving amiloride, a direct inhibitor of ENaC, should effectively lower BP, but in general, it is weakly antihypertensive 10 -13 and used primarily in combination with a thiazide diuretic for its potassium-sparing actions. 11In the patients described by Liddle et al, 4 triamterene, also an inhibitor of ENaC, lowered BP but only after sodium intake was severely restricted. Sodium has been shown to interfere with the ability of amiloride to inhibit sodium conductance in vitro, 14 and thus amiloride may not lower BP because modern diets are high in sodium. An alternative theory is that the secondary increase in aldosterone secretion that occurs in response to amiloride abrogates the ability of amiloride to prevent sodium reabsorption. In the present study, we examined the effect on BP of combining amiloride and spironolactone, a mineralocorticoid antagonist. Using a 2ϫ2 factorial study design, the BP responses to amiloride alone, spironolactone alone, the combination of amiloride and spironolactone, and placebo were compared in normotensive subjects. Methods SubjectsThe study used 20 whites and 20 blacks, age 18 to 30, from a cohort followed as part of a study of BP reg...

show abstract

“…However, one hour before each sensitization, these animals received a subcutaneous injection of amiloride (1 mg kg-1). This dose of amiloride was based on a previously established in vivo effective diuretic dose of amiloride (Combos et al, 1966). As in the control group, 24 h after the last sensitizing injection, animals in the experimental group were exposed to the inhalation challenge with aerosol of 0.1% ovalbumin.…”

Section: Effect Of Na' Replacementmentioning

confidence: 99%

The inhibition of sodium influx attenuates airway response to a specific antigen challenge

Souhrada

1988

British J Pharmacology

View full text Add to dashboard Cite

1 We have previously observed that manipulation of Na' availability during passive in vitro sensitization altered electrophysiological and contractile changes of airway smooth muscle cells.The purpose of this study was to establish whether interference with Na' influx during sensitization also influences the response of airway smooth muscle, both in vivo and in vitro, to a specific antigen challenge.2 Isolated segments of trachea which had been sensitized to ovalbumin in the presence of the Na' channel-blocking agent amiloride (10-M) showed no electrical or contractile response to ovalbumin in spite of their ability to respond to histamine (10-I M).3 Airway smooth muscle preparations sensitized to ovalbumin in a Na'-deficient medium failed to show any contractile response after exposure to ovalbumin and only a small depolarization of airway smooth muscle cells was detected. 4 Guinea-pigs were passively sensitized in vivo either in the absence of, or following pretreatment with, amiloride (1 mg kg-1 s.c.). These animals were then exposed to an ovalbumin inhalation challenge and both lung resistance (RL) and dynamic lung compliance (Cdy.) were measured.5 After an inhalation challenge of sensitized animals, we observed a significant increase in lung resistance (RL) achieving a maximum of 489% of the baseline values and a decrease in dynamic lung compliance (Cdyn). Twenty min after ovalbumin challenge Cdyf was equivalent to 20% of baseline values. 6 In animals pretreated with amiloride during sensitization, the inhalation challenge caused only a small increase in RL achieving a maximum increase of 148% of baseline values, and a small decrease in Cdy.. Twenty min after ovalbumin challenge Cdy. was equivalent to 98% of baseline values.7 We concluded that interference with Na' influx during both in vitro and in vivo sensitization attenuates the contractile and electrical responses of airway smooth muscle preparations or the changes in lung resistance and compliance observed after antigen challenge.

show abstract

Effects of MK-870 in Normal Subjects and Hypertensive Patients

Cited by 59 publications

References 4 publications

Amiloride hydrochloride in hypertensive patients.

Amiloride hydrochloride in hypertensive patients.

Blood Pressure Responses to Small Doses of Amiloride and Spironolactone in Normotensive Subjects

The inhibition of sodium influx attenuates airway response to a specific antigen challenge

Contact Info

Product

Resources

About