Metabolic degradation and synthesis of calcitriol in spontaneously hypertensive rat.
Plasma calcitriol concentration is unexpectedly low in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY) in view of previous findings of low plasma ionized calcium, hypophosphatemia, and hyperparathyroidism in SHR. Also, parathyroid hormone (PTH) and other exogenous stimuli cause a smaller increment in plasma calcitriol in SHR than in WKY. We investigated whether these differences in plasma calcitriol levels were due to decreased production rate (PR) or increased metabolic clearance rate (MCR) in SHR using the continuous infusion-isotope equilibration technique. In the basal state, MCR was 0.306 +/- 0.048 ml X min-1 X kg-1 in SHR and 0.284 +/- 0.026 ml X min-1 X kg-1 in WKY (P = NS). Estimated PR was lower in SHR (22.7 vs. 33.7 ng X day-1 X kg-1). With PTH infusion (3 U X h-1 X 100 g-1 for 20 h), MCR was 0.220 +/- 0.011 ml X min-1 X kg-1 in SHR and 0.256 +/- 0.017 ml X min-1 X kg-1 in WKY (P = NS). Measured PR was markedly lower in SHR (154 +/- 24 vs. 262 +/- 27 ng X day-1 X kg-1; P less than 0.02). Basal plasma PTH, total plasma calcium, and plasma inorganic phosphate were not different between SHR and WKY. Thus, SHR show diminished calcitriol production under basal condition and with PTH stimulation. MCR is not increased in SHR and does not appear to be influenced by PTH or the accompanying elevation in plasma calcium and calcitriol.
D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis / Q000097:blood*; D002118:Calcium / Q000097:blood; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood; D011921:Rats, Inbred WKY / Q000097:blood
D010281:Parathyroid Hormone; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium