IN-VIVO EFFECT OF CALCITRIOL ON CALCIUM-TRANSPORT AND CALCIUM-BINDINGPROTEINS IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The abnormal intestinal Ca2+ transport reported in spontaneously hyper tensive rats (SHR) has been attributed to decreased responsiveness to calcitriol. We reexamined this hypothesis by studying the calcitriol r egulation of SHR duodenal calbindin-D9K and calmodulin and the relatio n of calcitriol to Ca2+ uptake by isolated enterocytes. SHR and normot ensive Wistar-Kyoto (WKY) rats were injected with either 50 ng/d calci triol (vit-D) or vehicle alone (control) for 3 days. Decreased calbind in-D9K (P<.001) and cellular Ca2+ flux (P<.001) were observed in contr ol SHR. Calcitriol increased total cell and brush border calbindin-D9K (P<.0001); this variation paralleled plasma calcitriol levels in both strains. In contrast, Ca2+ flux, which increased in vit-D animals, re mained lower in SHR for plasma calcitriol levels similar to those in W KY rats. Immunoreactive calmodulin was similar in both strains whether assayed in total cell or brush border membranes. In contrast, when me asured by ligand blotting (Ca-45), calmodulin was lower in SHR than in WKY rats (P<.01), suggesting the existence of a calmodulin pool with reduced Ca2+ binding capacity in the hypertensive strain. Calcitriol h ad no effect on calmodulin in either strain. In conclusion, Ca2+ bindi ng protein regulation by calcitriol is normal in the SHR, and decrease d hormone responsiveness cannot account for the defective duodenal cal cium transport of this experimental model of hypertension.