Comparison of the hypotensive and diuretic effects of 1,4-dimorpholino-7-phenylpyrido[3,4]pyridazine (DS-511) and hydrochlorothiazide in Doca, renal and spontaneously hypertensive rats.

The hypotensive and diuretic activities of a new diuretic, 1,4-dimorpholino-7-phenylpyrido[3,4-d] pyridazine (DS-511), were compared with those of hydrochlorothiazide (HC) in DOCA, renal and spontaneously hypertensive rats. The results obtained were: 1. During the developing stage of DOCA-hypertension the daily treatment of rats with DS-511 and HC showed significant hypotensive action. During this period the diuretic activity of both agents was clear. 2. During the equilibrium stage of DOCA-hypertension the hypotensive action of DS-511 was indistinct despite its diuretic activity. The hypotensive and diuretic action of HC was not clear. 3. In renal-hypertensive rats the daily treatment of DS-511 and HC caused significant, but weaker hypotension than that in the developing stage of DOCA-hypertension. In these animals the diuretic activity of both agents was clear. 4. In spontaneously hypertensive rats the daily treatment with DS-511 and HC exhibited a similar hypotensive and diuretic action. 5. In all three kinds of hypertensive rats the diuretic activity of DS-511 was similar to that of HC in the excretion of urine and sodium, but the former was less kaliuretic than the latter.