On the hypocalciuric action of chlorothiazide.
Clearance experiments were performed in female mongrel dogs, either intact or thyro-parathy-roidectomized (T-PTX), under pentobarbital anesthesia, to examine the unusual hypocalciuric property of thiazide diuretics. The relationship between calcium clearance (C(Ca)) and sodium clearance (C(Na)) was determined in normal dogs, C(Ca) = 0.79 C(Na); constant infusion of chlorothiazide (CTZ) to provide drug concentrations in plasma of approximately 40 mug/ml modified this relationship; C(Ca) = 0.30 C(Na) (P < 0.001). The magnitude of the dissociating effect of CTZ on the urinary Ca/Na relationship was found to be most highly correlated with urinary drug concentration. Infusion of CTZ (1 mg/min) into one renal artery caused a unilateral decrease (25%) in C(Ca)/GFR while producing a unilateral increase (80%) in C(Na)/GFR. The same dose of CTZ in T-PTX dogs produced an increase in C(Na)/GFR without causing a change in C(Ca)/GFR. The defective response in T-PTX dogs could be ascribed to poor tubular secretion of the drug; when urinary drug concentrations were elevated in T-PTX dogs to the levels found in intact dogs (by infusing more drug), C(Ca)/GFR fell to an equivalent extent. T-PTX dogs showed substantially lower renal extraction of CTZ (42%) than intact dogs (57%); PTH administration to T-PTX dogs increased extraction toward normal (49%). The defective secretion of CTZ could not be attributed to either a decreased tubular maximum or a decreased renal blood flow.
D000818:Animals; D002118:Calcium / Q000097:blood / Q000652:urine; D002128:Calcium Metabolism Disorders / Q000139:chemically induced*; D002740:Chlorothiazide / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D010280:Parathyroid Glands / Q000502:physiology; D010710:Phosphates / Q000097:blood; D012039:Regional Blood Flow; D012077:Renal Artery; D012964:Sodium / Q000097:blood / Q000652:urine; D013961:Thyroid Gland / Q000502:physiology
D010710:Phosphates; D002740:Chlorothiazide; D005665:Furosemide; D012964:Sodium; D002118:Calcium