Antihypertensive effect of trichlormethiazide in spontaneously hypertensive rats

Antihypertensive and diuretic effects of trichlormethiazide (TCM) were investigated in the spontaneously hypertensive rats (SHR). The antihypertensive effect of TCM in an acute experiment was observed in male SHR only at a dose over 10 mg/kg given intraperitoneally and not in female SHR and normotensive Kyoto Wistar rats. In a subacute experiment (6 weeks), TCM retarded the development of hypertension in the male SHR loaded with 1% saline solution at an oral dose over 1 mg kg-1 day-1 and such had a diuretic effect. Oral administration of TCM and hydrochlorothiazide (HCT) at 10 mg kg-1 day-1 retarded the development of hypertension in the saline loaded female SHR to the same degree, but the relationship between antihypertensive and diuretic effects of both compounds was obscure. Except for decreases of water contents in the thoracic artery and wet weights of hearts, the electrolyte, uric acid, catecholamine and 5-hydroxytryptamine contents in the serum or/and organs were not affected by either TCM or HCT. It is concluded that the antihypertensive effect of TCM and HCT can be observed in SHR with a saline-load, and that the effect may be due to diuretic actions in the male. The relationship was not apparent in female SHR.