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Regression of left ventricular hypertrophy and control of hypertension in the spontaneously hypertensive rat (SHR): oxprenolol versus hydrochlorothiazide.

Idikio H, Fernandez PG, Triggle CR, Kim BK.

The control of hypertension with antihypertensive agents, in the spontaneously hypertensive rats (SHR) can result in regression of established cardiac hypertrophy. This study compared the effects of therapy with oxprenolol (Ox) and with hydrochlorothiazide (Htz) for (1) regression of established left ventricular hypertrophy (LVH) and (2) blood pressure control. Three groups of SHR and 3 comparable groups of Wistar-Kyoto (WKY) rats, matched for age, sex and body wt, were treated with tap water (Gp I), 60-200 mg hydrochlorothiazide kg-1 day-1 (Gp II) and 15-500 mg oxprenolol kg-1 day-1 (Gp III) for 13 weeks. Systolic and diastolic blood pressures (SBP, DBP mmHg), left ventricular wt/body wt ratio (LVwt/Bwt mg g-1) and left ventricular wall thickness (LVWT mm) were recorded. Oxprenolol lowered both systolic (mean +/- S.E. mmHg, 130 +/- 7 vs 189 +/- 8; P less than 0.01) and diastolic blood pressures (mean +/- S.E. mmHg, 104 +/- 6 vs 159 +/- 6; P less than 0.001) and caused regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.91 +/- 0.06 vs 3.10 +/- 0.09; P less than 0.05). In contrast, hydrochlorothiazide did not control blood pressure (mean +/- S.E. mmHg, 183 +/- 5 vs 189 +/- 6 and 152 +/- 5 vs 156 +/- 6), but it did cause regression of left ventricular hypertrophy (mean +/- S.E. mg g-1, 2.67 +/- 0.03 vs 3.10 +/- 0.09; P less than 0.01). Left ventricular wall thickness, measured in the mid-ventricular region, was significantly reduced only by hydrochlorothiazide (mean +/- S.E. mm, 2.76 +/- 0.06 vs 3.21 +/- 0.01; P less than 0.05). These results suggest that regression of left ventricular hypertrophy can occur with or without control of hypertension in the SHR.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6219850&dopt=Abstract hydrochlorothiazide Microzide



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Effect of long-term antihypertensive therapy on cardiac anatomy in patients with essential hypertension.

Drayer JI, Weber MA, Gardin JM, Lipson JL.

M-mode echocardiography was used in 12 patients with essential hypertension to study changes in cardiac anatomy during long-term therapy with hydrochlorothiazide (50 to 100 mg) and alpha-methyldopa (500 to 1,750 mg). Echocardiographic examination was performed after six weeks of treatment with hydrochlorothiazide alone and after four to six weeks, six months, and nine months of treatment with both hydrochlorothiazide and alpha-methyldopa. Hydrochlorothiazide alone induced a small, and not significant, change in blood pressure (from 157 +/- 16 (SD)/105 +/- 9 to 150 +/- 14/101 +/- 5 mm Hg). Changes in echocardiographic parameters of cardiac anatomy were not observed during short-term diuretic therapy. Addition of alpha-methyldopa further reduced blood pressure (to 133 +/- 11/90 +/- 6 mm Hg, p less than 0.001), which was maintained throughout the study. Gradual decreases in diastolic septal thickness (from 10.9 +/- 1.1 to 9.5 +/- 1.0 mm, p less than 0.01), relative wall thickness (from 0.40 +/- 0.06 to 0.36 +/- 0.06, p less than 0.05) and left ventricular cross-sectional area (from 18.9 +/- 2.9 to 17.3 +/- 2.6 cm2, p less than 0.05) were observed. Posterior wall thickness did not change significantly during the study. The results provide evidence for regression of echocardiographic parameters of cardiac muscle mass during long-term antihypertensive treatment with a diuretic and a centrally-acting sympatholytic drug. Regression of left ventricular mass was not clearly related to changes in casual blood pressure. However, patients who showed a decrease in septal thickness tended to have a greater decrease in systolic blood pressure than those in whom septal thickness did not change during therapy. Moreover, patients in whom a decrease in left ventricular transverse dimension was observed, had a greater decrease in both systolic and diastolic blood pressure than those in whom left ventricular diastolic dimension did not change.

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Monotherapy in mild to moderate hypertension: comparison of hydrochlorothiazide, propranolol and prazosin.

Inouye I, Massie B, Benowitz N, Simpson P, Loge D, Topic N.

There has been recent interest in using nondiuretic drugs as initial antihypertensive therapy. Therefore, a study was designed to compare the efficacy and the effects on left ventricular function of hydrochlorothiazide, propranolol and prazosin in 13 patients with mild to moderate hypertension. After a 4-week washout period, patients were treated serially with each drug in a randomized order for 2 months each. Dosages were titrated until the patient showed a sitting diastolic blood pressure less than or equal to 90 mm Hg or to a maximum dosage of 100 mg/day of hydrochlorothiazide, 320 mg of propranolol and 20 mg of prazosin. Blood pressure was measured, plasma catecholamine concentrations were assayed and radionuclide determinations of rest and exercise left ventricular function and volume were made at the end of each period as well as after a second 1-month washout period at the end. In the sitting and standing positions, systolic and diastolic blood pressure control was equivalent for all 3 drugs. Goal blood pressure was achieved in 10 of 13 patients receiving hydrochlorothiazide, in 8 of 12 receiving propranolol and in 9 of 13 on prazosin. Importantly, 3 of 4 patients not controlled with prazosin, 5 of 6 uncontrolled with propranolol and 2 of 3 whose blood pressure was not reduced by hydrochlorothiazide were controlled when receiving 1 of the other medications. None of the drugs changed rest or exercise ejection fraction or volume, and side effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of sodium bicarbonate and hydrochlorothiazide on the hypercalciuric action of 1,25(OH)2D3 in the rat.

Goulding A, Campbell DR.

The hypercalcaemic and hypercalciuric effects of high doses of 1,25(OH)2D3 (50 nanograms per day for 7 days) were studied in rats taking a standard basal diet, with or without supplements of NaHCO3 (4.5 mmoles per day), hydrochlorothiazide (10 milligrams per kilogram body weight per day), or both NaHCO3 and hydrochlorothiazide. 1,25(OH)2D3 elevated plasma and urinary calcium values. The degree of hypercalcaemia elicited was similar in all groups but hypercalciuria was less in groups given NaHCO3 or hydrochlorothiazide. It is suggested that NaHCO3, like thiazide diuretics, might be useful in limiting hypercalciuria in stone-formers with elevated plasma levels of 1,25(OH)2D3.

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Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide.

Inouye IK, Massie BM, Benowitz N, Simpson P, Loge D.

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6375339&dopt=Abstract hydrochlorothiazide Microzide