Renal hemodynamics and sodium excretion after acute and chronic administration of cicletanine in normotensive and hypertensive subjects.
We examined the effects of two therapeutic oral (p.o.) doses of cicletanine (50 and 100 mg daily) on renal hemodynamics and segmental tubular handling of sodium. Six normotensive (NT) healthy subjects (group 1) received 50 mg cicletanine, and 12 moderately hypertensive (HT) patients with normal sodium diet and randomly divided into two groups of 6 were treated either with cicletanine 50 mg (group II) or with cicletanine 100 mg (group III). Studies were performed both acutely and after 4 weeks of cicletanine administration. After 28-day treatment, blood pressure (BP) was significantly reduced in HT patients. In NT subjects (group I) and HT patients (groups II and III), acute administration of cicletanine 50 or 100 mg at day 0 did not significantly modify glomerular filtration rate (GFR) or renal blood flow (RBF), but markedly increased fractional excretion of Na (FENa) by 67% in group I and by 62 and 135% in groups II and III, respectively. Fractional distal reabsorption of Na (FDRNa) was significantly reduced in the three groups after cicletanine administration. After 4-weeks treatment, GFR and RBF were not significantly modified. The increase in FeNa and decrease in FDRNa were of the same magnitude as that at day 0. No major changes occurred in hormonal profile [renin, aldosterone, atrial natriuretic factor (ANF)]. Even at low doses, cicletanine has a natriuretic effect in NT and HT subjects. Unchanged fractional reabsorption of lithium and a significant decrease in FDRNa in the three groups suggest that this natriuretic effect occurs at the distal tubule.
Moulin
B
B
Department of Nephrology, University of Rouen, Paris, France.
Fillastre
J P
JP
Godin
M
M
Coquerel
A
A
Decoopman
E
E
D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D004573:Electrolytes; D011725:Pyridines; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; C038068:cicletanine; D012083:Renin