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Effects of antihypertensive drugs on heart and resistance vessels.

Kobayashi H, Sano T, Tarazi RC, Fouad-Tarazi FM.

Department of Heart and Hypertension, Cleveland Clinic Foundation, Ohio 44195-5069.

STUDY OBJECTIVE - The aim of the study was to examine the effects of antihypertensive drugs on heart and resistance vessels to see whether regression of peripheral vascular hypertrophy accompanies reduction in cardiac mass. DESIGN - Matched groups of spontaneously hypertensive and control rats were treated for 12 weeks with captopril (average dose 65 mg.kg-1.d-1) or hydrochlorothiazide (73 mg.kg-1.d-1) and compared to untreated groups. Perfusion pressure, which has been validated as an index of hypertrophy of resistance vessels, was determined in hind limbs of pithed rats at constant blood flow and maximum vasodilatation. SUBJECTS - Experimental animals were 14 week old male spontaneously hypertensive (SHR) rats (n = 41) and strictly age matched Wistar Kyoto rats (n = 12). SHR rats were assigned at random to three groups: (a) captopril treated (n = 15), (b) hydrochlorothiazide treated (n = 15), (c) control (n = 11). MEASUREMENTS and RESULTS - Mean perfusion pressure was 29.5(SEM 0.4) mm Hg in untreated Wistar Kyoto rats and 37.4(0.5) mm Hg in untreated SHR rats. In comparison with untreated SHR rats, treatment with captopril lowered blood pressure, perfusion pressure [35.2(0.3) v 37.4(0.5) mm Hg, p less than 0.01)], and left ventricular to body weight ratio [2.28(0.03) v 2.63(0.05) mg.g-1, p less than 0.01)]. Treatment with hydrochlorothiazide also lowered blood pressure but had no significant effect on left ventricular weight to body weight ratio [2.54(0.04)]. However, perfusion pressure was reduced to 35.3(0.5) mm Hg, p less than 0.01. CONCLUSIONS - For equal regression of vascular hypertrophy, captopril and hydrochlorothiazide had different effects on regression of left ventricular hypertrophy. Thus left ventricular and vascular structural changes may respond differently to the same drug in the same animal.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2183938&dopt=Abstract hydrochlorothiazide Microzide



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Effectiveness and safety of captopril in Sudanese hypertensive patients.

Abdel Rahim IM, Elsaid MM, Ali MM.

Faculty of Medicine, Gezira University, Wad Medani, Sudan.

This study reports on the effectiveness, safety and acceptability of captopril in 36 Sudanese patients, who were classified as resistant, moderate to severe and mild according to initial diastolic blood pressure and history of treatment. The patients were titrated against a six-step captopril treatment regime with or without hydrochlorothiazide and reserpine. The median follow up period was 11.6 month. The initial median pre-treatment blood pressure was 159/101, 182/120 and 217/130 and at the end of study 125/77, 120/74 and 165/95 for the mild, severe and resistant groups respectively. Tolerance was good and side effects were mild and similar to others reported in literature. The effective daily treatment was 25-50 mg captopril for mild hypertension, 50 to 100 mg captopril with 50 mg hydrochlorothiazide for severe hypertension while it was 225 mg captopril with 50 to 100 mg hydrochlorothiazide and a need for a third drug in 30% of patients in the resistant group. These results reveal normal responsiveness to captopril among black Sudanese patients with good tolerance and safety.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2187093&dopt=Abstract hydrochlorothiazide Microzide



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HPLC-photolysis-electrochemical detection in pharmaceutical analysis: application to the determination of spironolactone and hydrochlorothiazide in tablets.

Bachman WJ, Stewart JT.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Georgia, Athens 30602.

To extend the applicability of electrochemical detection in pharmaceutical analysis, an on-line postcolumn photochemical reactor is used to produce electroactive photoderivatives of selected cardiovascular drugs. This system is applied to the analysis of dosage forms containing spironolactone in both single-component formulation and in combination with hydrochlorothiazide. The pH of the mobile phase and irradiation time within the reactor are optimized to produce maximum amperometric response. Spironolactone, hydrochlorothiazide, and 4-amino-6-chloro-1,3-benzenedisulfonamide, the synthetic precursor and hydrolysis product of hydrochlorothiazide, are separated by reversed-phase chromatography on a 5-microns cyano bonded phase column within nine minutes by using a methanol-phosphate buffer mobile phase. Minimum detectable levels are in the low ng range.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2273066&dopt=Abstract hydrochlorothiazide Microzide



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Restoration of arterial baroreflex function contributes to organ protection in spontaneously hypertensive rats treated with long-term hydrochlorothiazide mixture.

Lu ZA, Xie HH, Xu LP, Yin AF, Miao CY, Su DF.

Department of Pharmacology, Basic Medical College, Second Military Medical University, Shanghai, China.

1. Hydrochlorothiazide mixture (HCTM) is widely used in China for the treatment of hypertension. This mixture consists of hydrochlorothiazide, triamterene, reserpine, hydralazine and chlordiazpoxide, with small (one-third to one-fifth of normal) doses of each drug. The present study was designed to investigate the effects of this mixture on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage in spontaneously hypertensive rats (SHR). 2. The HCTM was mixed in the rat chow and rats were treated for 4 months. After treatment, rats were catheterized and their blood pressure, BPV and BRS were measured in the conscious state. Organ damage was examined after these measurements had been completed. 3. It was found that HCTM not only decreased blood pressure and BPV, but also ameliorated impaired BRS in SHR. The HCTM had an obvious effect on organ protection in SHR. 4. The HCTM prevented left ventricular hypertrophy and this effect was mainly related to a decrease in systolic blood pressure. The effects of HCTM on preventing renal atrophy were mainly determined by BRS. Baroreflex sensitivity was the most important determinant for predicting organ damage in HCTM-treated SHR. 5. In conclusion, long-term treatment of rats with HCTM prevented hypertensive organ damage. Restoration of arterial baroreflex function contributes to organ protection in SHR treated in the long term with HCTM.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12542453&dopt=Abstract hydrochlorothiazide Microzide



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Effects of reduction in dose and discontinuation of hydrochlorothiazide in patients with controlled essential hypertension.

Kochar MS, Landry KM, Ristow SM.

Hypertension Section, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295.

We studied the effects of a reduction in dose of hydrochlorothiazide from 50 to 25 mg/d, and its discontinuation for up to 22 months in 36 well-controlled hypertensive patients. Hydrochlorothiazide was discontinued if the diastolic blood pressure remained less than or equal to 94 mm Hg after a 6-month period on the lower dose of hydrochlorothiazide. No other changes were made in medications or diet. Sitting systolic blood pressure rose from 135 +/- 15 mm Hg to 140 +/- 14 mm Hg on reduction of the hydrochlorothiazide dose and rose still further to 145 +/- 20 mm Hg on discontinuation. Even greater increases in standing blood pressure were observed. There were no significant effects on the diastolic blood pressure with reduction of dose or discontinuation of hydrochlorothiazide. A significant decrease in the serum uric acid and a rise in serum potassium occurred. There were no changes in serum glucose or lipids on reduction in the dose of hydrochlorothiazide; whereas, with discontinuation, the serum lipids and hemoglobin A1C fell significantly. These results suggest that the benefits of a reduced dose of hydrochlorothiazide may not be as great as considered heretofore.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2331182&dopt=Abstract hydrochlorothiazide Microzide