[Antihypertensive and related hemodynamic effects of a thiazide in desoxycorticosterone (DOC)/saline hypertensive...

Antihypertensive and related hemodynamic effects of trichlormethiazide (TCM), a thiazide, in DOC/saline hypertensive rats were investigated. To prepare hypertensive rats, 7-week-old male Wistar rats were subjected to nephrectomy of the left kidney, subcutaneously administered DOC (5 mg/kg X 3 times/week, or a 25-mg tablet), and given 1% saline solution as drinking water. When the systolic blood pressure of the rats reached about 200 mmHg, once-a-day oral administration of an arabic gum suspension of TCM was started. The results were: 1) Oral administration of TCM at no less than 3 mg/kg/day showed a dose-dependent, lasting antihypertensive effect throughout the experimental periods. 2) TCM administration effectively prevented the appearance of malignant hypertensive symptoms such as body weight loss, ischemia of the ocular fundus, and slight paralysis of extremities with the following pathological changes: hyalinization and fibrinoid necrosis of renal arteries and glomeruli, degeneration of renal tubules, and cardiac hypertrophy. 3) Although TCM had no effect throughout the experimental periods on the cardiac output (CO), which was determined by a modified dye-dilution method, total peripheral resistance (TPR) decreased from the first week of TCM administration. The antihypertensive effect of TCM in DOC/saline hypertensive rats is presumed to be associated with the decrease of TPR from early stages of therapy.