title: Pathogenesis of hypercalciuria in spontaneously hypertensive rats.
abstract: The etiology of hypercalciuria remains unknown in spontaneously hypertensive rats (SHR). In order to differentiate absorptive versus renal hypercalciuria, serial measurements of urinary calcium (UCaV) excretion were made weekly under fasting (3-hour urine collection) and after oral administration of CaCl2 (50 mg/100 g; 4-hour urine collection) from age 8 to 14 weeks in SHR (n = 14) and normotensive Wistar Kyoto rats (WKY; n = 14). Fasting UCaV was significantly greater in WKY than in SHR throughout the periods of observation. In contrast, after oral Ca loading UCaV was greater in SHR after 13 weeks of age (13 weeks: SHR UCaV = 954 micrograms/mg creatinine, WKY UCaV = 541 p less than 0.01; 14 weeks: SHR UCaV = 988 micrograms/mg creatinine, WKY UCaV = 534, p less than 0.01). Fasting urinary cyclic adenosine monophosphate (AMP) excretion was not different between WKY and SHR. However, cyclic AMP excretion of SHR, but not WKY, was decreased after calcium loading when compared to the fasting values. The cyclic AMP was also significantly lower in SHR than in WKY rats after calcium loading. Calcium handling by the kidney was not different between SHR and WKY with or without parathyroidectomy. Calcium disposition kinetic studies were performed on these animals at age 15 and 16 weeks. No significant difference of intravenous 45Ca was observed between WKY (n = 6) and SHR (n = 6) in total plasma clearance, nonrenal clearance, biologic half-life, and elimination rate constant from the central compartment. However, the WKY had a significantly greater renal clearance of 45Ca than the SHR (0.48 +/- 0.04 vs. 0.24 +/- 0.02 ml/n, p less than 0.001). Since tissue disposition of intravenous 45Ca was not different between WKY and SHR, the increased renal excretion of calcium after oral administration in SHR, therefore, reflects increased intestinal absorption of calcium. Correction of established hypertension did not abolish the hypercalciuria. We believe that increased gastrointestinal absorption of calcium is responsible for the hypercalciuria in SHR.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000652:urine*; D006973:Hypertension / Q000652:urine; D007263:Infusions, Parenteral; D007408:Intestinal Absorption; D007700:Kinetics; D010280:Parathyroid Glands / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000652:urine*; D011919:Rats, Inbred Strains / Q000652:urine*; D011921:Rats, Inbred WKY / Q000652:urine; D012964:Sodium / Q000652:urine; D013965:Thyroidectomy
chemical_list: D010758:Phosphorus; D012964:Sodium; D002118:Calcium