ozolinone and Hypertension

The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n = 6) and impaired kidney function (n = 6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n = 4) and varying degrees of renal impairment (n = 11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (-12 mm Hg) and diastolic (-9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antihypertensive Agents; Diuretics; Female; Furosemide; Humans; Hypertension; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Norepinephrine; Renin; Thiazoles

The inhibition of the renin-angiotensin system by captopril was used in pentobarbital-anesthetized dogs to confirm that the vasoconstrictive action of endorenally synthesized angiotensin II predominates on the efferent glomerular arteriole. Ozolinone is a loop diuretic with two isomers. Only (-)- ozolinone is diuretic, whereas both isomers have a renal vasodilatory effect which predominates on the efferent glomerular arteriole. Only the diuretic isomer increases renin release. The renin hypersecretion is simultaneous with recovery from the initial fall in filtration fraction, because of postglomerular vasodilatation. This recovery does not occur with (+)- ozolinone and is inhibited by pretreatment with captopril. This confirms that vasoconstrictive action of angiotensin II predominates on the efferent glomerular arteriole. Such a vasoconstrictive effect might affect blood flow in the vasa recta, which arise from the efferent arterioles of juxtamedullary glomeruli. This action might enable the renin-angiotensin system to participate in the control of renal medullary blood flow and urinary concentration.

Topics: Animals; Captopril; Diuresis; Diuretics; Dogs; Furosemide; Glomerular Filtration Rate; Humans; Hypertension; Kidney Concentrating Ability; Kidney Glomerulus; Male; Osmolar Concentration; Proline; Propranolol; Rats; Renal Circulation; Renin; Renin-Angiotensin System; Stereoisomerism; Thiazoles; Vasoconstriction