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Effect of chronic diuretics on epinephrine-induced ventricular arrhythmias: a comparison of hydrochlorothiazide and amiloride in the rat.

Rabkin SW, Roob O.

The purpose of this study was to determine if chronic administration of the diuretics hydrochlorothiazide and amiloride alters the response to catecholamine-induced ventricular arrhythmias. The protocol consisted of four groups of Wistar rats. Group I, or control group, received daily subcutaneous injections of saline; group II received hydrochlorothiazide, 100 mg/kg/day s.c.; group III received amiloride, 0.5 or 1.0 mg/kg/day s.c.; and group IV received amiloride, 0.5 mg/kg/day, plus hydrochlorothiazide, 100 mg/kg/day. The treatment period lasted 18 days. After completion of the treatment period, under pentobarbital anesthesia, epinephrine was infused and the electrocardiogram and blood pressure recorded. Hydrochlorothiazide produced a significant (p less than 0.05) leftward shift in the dose-response relationship, that is, a smaller epinephrine concentration produced earlier onset of ventricular arrhythmias and mortality from fatal ventricular arrhythmias. Amiloride, at the higher dose, significantly (p less than 0.05) shifted to the right the dose-response relationship between epinephrine and occurrence of arrhythmias--i.e., a larger epinephrine dose was necessary to produce the same amount of arrhythmias. There were no significant differences in heart rate or blood pressure responses to epinephrine among the four groups. Serum and myocardial electrolytes were measured in a separate group of rats that did not receive epinephrine. There were no significant differences among groups for myocardial electrolytes. After hydrochlorothiazide administration, serum calcium and magnesium were decreased and bicarbonate was increased compared with the control group. In the amiloride group, only serum sodium was significantly changed, being slightly increased. This suggests that serum electrolyte levels may account for the effects of hydrochlorothiazide but do not account for the effect of amiloride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2441176&dopt=Abstract hydrochlorothiazide Microzide



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Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension.

Quintanilla AP, Finn M, Weffer MI, Del Greco F.

Section of Nephrology-Hypertension, VA Lakeside Medical Center, Chicago, IL 60611.

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2822824&dopt=Abstract hydrochlorothiazide Microzide



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Regression of hypertrophy in small resistance vessels.

Sano T, Tarazi RC.

Research Division, Cleveland Clinic Foundation, Cleveland, Ohio.

Many studies have documented regression of left ventricular hypertrophy following blood pressure control by some antihypertensive agents but not by others. To determine whether similar differences in regression of wall thickening also occur in resistance vessels during treatment, matched control groups of spontaneously hypertensive rats (SHR) were treated for 12 weeks with either hydralazine or captopril + hydrochlorothiazide and compared with untreated SHR and Wistar-Kyoto rats (WKY). Perfusion pressure was then determined in the hind-limbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilatation as an index of thickening (hypertrophy) of resistance vessel walls. Treatment with hydralazine or captopril + hydrochlorothiazide controlled blood pressure equally in SHR but had significantly different effects on both left ventricular hypertrophy and resistance vessels. Perfusion pressure was reduced from 37.4 +/- 0.5 mmHg to 33.9 +/- 0.5 mmHg (P < 0.01) with captopril + hydrochlorothiazide but only marginally to 35.9 +/- 0.3 mmHg with hydralazine (P < 0.05 at some levels of flow and P > 0.05 at others). Left ventricular weight was significantly reduced by captopril + hydrochlorothiazide (2.02 +/- 0.02 versus 2.63 +/- 0.05 mg/g, P < 0.01) but only to 2.44 +/- 0.05 by hydralazine. Significant correlations were found both before and following treatment between perfusion pressure and left ventricular weight (r = 0.59, P < 0.01) but not between either of these two parameters and arterial pressure. Thus, despite equal blood pressure control, thickening of resistance vessel walls regressed more with captopril + hydrochlorothiazide than with hydralazine, suggesting that vascular hypertrophy-like left ventricular hypertrophy is not determined by blood pressure levels alone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2856775&dopt=Abstract hydrochlorothiazide Microzide



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Effect of 8-phenyltheophylline, enprofylline and hydrochlorothiazide on glycerol-induced acute renal failure in the rat.

Yates MS, Bowmer CJ, Kellett R, Collis MG.

Department of Pharmacology, University of Leeds, UK.

The adenosine antagonist 8-phenyltheophylline (8-PT) is a diuretic in normal rats and can ameliorate glycerol-induced acute renal failure (ARF) in this species. To define which action of 8-PT is important in its salutary effect in ARF, we have compared its effects with those of enprofylline (a xanthine with little affinity for adenosine receptors) and with those of the tubular diuretic hydrochlorothiazide. In one series of experiments, groups of rats with ARF of 24 h duration were given a single dose of drug or vehicle. Only 8-PT enhanced urine volume when compared with the vehicle-treated group. In a second set of experiments, groups of glycerol-injected rats received drug or vehicle treatment (i.p.) twice daily for 2 days. Rats which received a course of 8-PT treatment had significantly lower plasma urea and creatinine concentrations, a higher glomerular filtration rate, a lower kidney weight and improved kidney morphology when compared with vehicle-treated rats. The only beneficial effect noted after enprofylline treatment was an improved kidney morphology. Hydrochlorothiazide treatment compared with vehicle treatment did not ameliorate any index of renal function but resulted in significant elevations in plasma urea and creatinine levels. The inability of enprofylline or hydrochlorothiazide to mimic the effects of 8-PT in ARF indicate that the effects of 8-PT are probably associated with adenosine receptor blockade and not with a tubular diuretic action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2891817&dopt=Abstract hydrochlorothiazide Microzide



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Potassium bicarbonate supplementation blocks the hypocalciuric response to hydrochlorothiazide in rats.

Goulding A, McIntosh J.

Bicarbonate salts and thiazide diuretics each lower urinary calcium excretion. This study was undertaken to compare the effects of administering oral sodium or potassium bicarbonate supplements (4.5 mmol./day of each salt) each with or without hydrochlorothiazide (10 mg./kg. body weight/day) on urinary calcium excretion in rats. Urinary calcium decreased (p less than 0.01) by about 50 per cent after sodium bicarbonate supplementation and potassium bicarbonate supplementation. The hypocalciuric response to each bicarbonate salt was similar. However, although hydrochlorothiazide depressed urinary calcium in rats consuming sodium bicarbonate, rats receiving equimolar supplements of potassium bicarbonate did not lower urinary calcium when given hydrochlorothiazide, despite evidence of the expected thiazide-mediated diuresis. It is concluded that in the rat potassium bicarbonate loading blocks the ability of hydrochlorothiazide to lower urinary calcium excretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2985833&dopt=Abstract hydrochlorothiazide Microzide