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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a group of hypertensive patients it has been shown that moderate sodium chloride restriction has a hypotensive effect that is similar to that produced by thiazide diuretics. Blood pressure changed in relation to body weight in individual patients, and appeared to correlate with their sodium balance. The more a patient was depleted of sodium, the lower was the blood pressure. The serum potassium level fell with the use of thiazide diuretics, but in this group of patients there was little change in total body potassium content. The fall in serum potassium level appeared to relate to a shift into the cells due to the accompanying alkalosis. Potassium supplementation appeared to have had little effect and was unnecessary for most patients who were given diuretics for hypertension. Amiloride corrected the alkalosis and restored the serum potassium level to normal.
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PMID:Sodium restriction and thiazide diuretics in the treatment of hypertension. 115 72

This study investigated the ability of two diuretics, amiloride and frusemide, to prevent the development of ACTH induced hypertension in conscious sheep. Infusion of amiloride (20 mg/day) or frusemide (50 mg/day) for three days into normotensive sheep did not have any significant effects on blood pressure. Amiloride blocked ACTH-induced hypertension and the sodium retention and hypokalemia which is usually associated with ACTH administration. Frusemide failed to completely block the hypertension and potassium loss, however it blocked the transient initial urinary sodium retention associated with ACTH-induced hypertension. As frusemide failed to completely block the hypertension it is unlikely that the amiloride effect is due primarily to effects on urinary Na excretion. It is possible that amiloride is exerting its antihypertensive effects by blocking sodium channels.
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PMID:Amiloride blocks the onset of ACTH-induced hypertension in the sheep. 217 63

The sodium-hydrogen (Na+/H+) antiport is electroneutral and amiloride-sensitive. It exchanges Na+ for H+ with a coupling ratio of 1:1 and therefore, it has important cellular functions: intracellular pH and cell volume regulation, control of the cell differentiation and growth. Its activity is increased in hypertension. The responsibility of the Na+/H+ antiport in essential hypertension may result in increased vascular tone and vascular hyperplasia. Amiloride is a specific inhibitor of this exchanger but under physiological conditions, very high concentrations of this drug (that are unlikely to be attained in vivo) are required to inhibit the activity of the Na+/H+ antiport. Certain of its analogues are much more potent in vitro than amiloride. Therefore, the Na+/H+ antiport may become a target for new antihypertensive drugs.
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PMID:[The Na+/H+ antiport: a target for new antihypertensive agents]. 255 Oct 56

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
Hypertension 1989 Jun
PMID:Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line. 256 5

Amiloride (100-400 micrograms) injected intra-arterially into the dog forelimb perfused at constant flow produced a prompt but transient dose-dependent decrease in perfusion pressure. Intravenous injection lowered systemic arterial pressure, but effects were small and transient except in doses exceeding 10 mg. We tested 11 analogues of amiloride, 3 other diuretics, and a hypotensive imidazopyrazine for vasodilator activity in the dog forelimb and found one analogue, 6-iodo-amiloride, with twice the activity of amiloride. Intravenous injection of 3 mg of 6-iodo-amiloride promptly decreased systemic arterial pressure and forelimb perfusion pressure 65 and 47 mm Hg respectively. The decreases with 3 mg of amiloride were only 5 and 23 mm Hg respectively. Intravenous infusion of 17 to 77 mg of 6-iodo-amiloride produced diuresis, natriuresis, and antikaliuresis and, with the higher doses, hypotension. The latter occurred promptly on starting the infusion and was sustained for the duration of the infusion. Wistar rats responded to an intravenous infusion of 0.38 mg/100 g in 11 minutes in the same manner. In the spontaneously hypertensive rat, this same dose produced a large, sustained antihypertensive effect with little change in the urinary parameters. These studies indicate that 6-iodo-amiloride is a vasodilator and a vasodepressor as well as natriuretic and diuretic in the normal dog and rat and that it produces a sustained, large fall in blood pressure, independently of urinary effects, in the spontaneously hypertensive rat. These results suggest that 6-iodo-amiloride and other sodium channel blockers might be useful as vasodilatory antihypertensive agents, particularly in those types of hypertension characterized by increased vascular smooth muscle cell permeability to sodium.
Hypertension
PMID:Sodium channel blockers are vasodilator as well as natriuretic and diuretic agents. 258 96

The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics. The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml.min-1, amiloride; and from 418 to 157 ml.min-1, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng.ml-1, Css,max; from 2 to 8 ng.ml-1, Css,min; and from 4 to 14 ng.ml-1, Cav; Hydrochlorothiazide: from 184 to 651 ng.ml-1, Css,max; from 31 to 121 ng.ml-1, Css,min; and from 89 to 273 ng.ml-1, Cav). The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r = 0.62, young; r = 0.72, elderly). As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.
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PMID:The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly. 279 71

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demonstrated little sodium-dependent adenosine triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5'-triphosphate.
Hypertension 1987 Nov
PMID:Membrane biochemistry of the ouabain-resistant potassium transport system. 282 73

We report a case of diffuse interstitial pulmonary disease in a 73 year old woman treated for moderate hypertension for one year with the combination of hydrochlorothiazide (50 mg/day) and Amiloride (5 mg/day). The bronchoalveolar lavage showed a neutrophilia of 23% and a 5.5% eosinophilia. The absence of any other aetiological factor and the favourable outcome on cessation of the sole medication incriminate the latter as an aetiological agent in this interstitial pneumonitis.
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PMID:[Subacute pneumopathy caused by hydrochlorothiazide. Cytologic study of the broncho-alveolar lavage]. 378 31

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.
Hypertension
PMID:Inhibition of furosemide-induced increases in plasma renin activity by amiloride. 635 81

We studied the role of increased Na+ permeability on the increased responsiveness to ouabain and to K+-free solution in aortas from DOCA hypertensive rats. Helically cut strips from DOCA hypertensive and normotensive control rats were mounted in a muscle bath for recording isometric force. In response to ouabain, aortas from DOCA hypertensive rats were significantly more sensitive and developed a greater maximal force than aortas from control rats. The rate of force development in response to K+-free solution was significantly faster in aortas from DOCA hypertensive rats as compared to those from control rats. Monensin (10(-5)M), a Na+ ionophore, increased the contractile response to ouabain and the rate of force development in response to K+-free solution in both DOCA hypertensive and control aortas. Amiloride (3 X 10(-5) M), a Na+ channel blocker, decreased the contractile response to ouabain and the rate of force development to a K+-free solution in both the DOCA hypertensive and control aortas, but the magnitude of decrease was greater in aortas from DOCA hypertensive rats. Thus, a Na+ ionophore causes the control aortas to perform like those from DOCA hypertensive rats, and a Na+ channel blocker causes aortas from DOCA hypertensive rats to perform like those from control rats. It is concluded that the difference between the two is that the smooth muscle of aortas from DOCA hypertensive rats is more permeable to Na+ than is that from control rats.
Hypertension
PMID:Functional evidence for increased sodium permeability in aortas from DOCA hypertensive rats. 672 74


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