Effect of indapamide on volume-dependent hypertension, renal haemodynamics, solute excretion and proximal nephron fractional reabsorption in the dog.
Indapamide, a newly developed antihypertensive agent with modest diuretic properties, reduced mean arterial pressure toward normal in dogs made hypertensive with salt and DOCA, while low-dose furosemide (0.1 mg per day) and hydrochlorothiazide (1 and 50 mg per day) did not result in similar degrees of blood pressure control. Indapamide, low-dose furosemide and hydrochlorothiazide treatment all resulted in similar decreases in body weight suggesting that the antihypertensive effect of indapamide occurs through a mechanism independent of contraction of extracellular fluid volume. Intravenous indapamide at doses of 0.3, 1.0 and 3.0 mg/kg caused progressive increases in sodium, potassium and chloride excretion when urine losses were replaced by isotonic saline to prevent extracellular fluid volume contraction. Only at 3.0 mg/kg did plasma potassium decrease significantly (2.92 +/- 0.03 to 2.69 +/- 0.05 mmol/l; p less than 0.05). Neither glomerular filtration rate (GFR) nor renal blood flow (flowmeter) decreased in a dose-related manner; however, effective renal plasma flow assessed by para-aminohippurate clearance did decrease about 15% at the highest dose (p less than 0.05). Proximal re-collection micropuncture studies demonstrated decreased proximal reabsorption. Cortical diluting segment reabsorption was decreased, but CNa + CH2O/GFR increased from 7% to 11% (p less than 0.05). These results indicate that, at doses up to 3.0 mg/kg, indapamide causes a natriuresis which is modest and similar to that seen with thiazides. No decrease in GFR or renal blood flow was observed. This drug apparently exerts a natriuretic effect through an inhibition of solute reabsorption in both the proximal nephron and the cortical diluting segment.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000503:physiopathology*; D007190:Indapamide / Q000008:administration & dosage*; D007668:Kidney / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D004232:Diuretics; D004573:Electrolytes; D006852:Hydrochlorothiazide; D005665:Furosemide; D012964:Sodium; D007190:Indapamide; D011188:Potassium