Calcium and sodium transport and vitamin D metabolism in the spontaneously hypertensive rat.
Serum ionized calcium levels are lower and immunoreactive parathyroid hormone levels are higher in the spontaneously hypertensive (SH) rat than in the normotensive Wistar-Kyoto (WKy) control. We postulated that there is either a defect in the regulation of vitamin D metabolism by parathyroid hormone or that the gut target organ for vitamin D in the SH rat is unresponsive. To test these hypotheses we measured serum concentrations of vitamin D metabolites and intestinal transport of calcium and sodium. Compared with that of WKy controls, in vitro calcium transport by duodenal sacs of the SH rat was decreased (P less than 0.001) at 5 wk, before the development of hypertension, and at 12 wk, after hypertension was well established. When measured in vivo in the most proximal 20 cm of small intestine, maximum velocity (Vmax) for calcium transport was decreased (P less than 0.05) and net absorption of sodium and water was increased (P less than 0.05) in SH rats as compared with WKy rats. Vmax for calcium transport was also decreased (P less than 0.05) in the most distal 20 cm of small intestine of SH rats, but net sodium and water transport were the same in SH and WKy rats. At 12 wk, serum concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] was the same in both SH and WKy groups, but its precursor, 25-hydroxycholecalciferol, was increased (P less than 0.05) in the SH rat. We conclude that in the SH rat: (a) the concentration of 1,25-(OH)2D3 is inappropriately low in relation to the elevated immunoreactive parathyroid hormone and the depressed calcium absorption, suggesting a defect in the regulation of vitamin D metabolism; and (b) the depressed calcium absorption, in the setting of normal concentrations of [1,25-(OH)2D3], demonstrates unresponsiveness of the gut to vitamin D and may explain in part the low serum ionized calcium found in earlier studies. The presence of these abnormalities before we found a significant difference in blood pressure suggests that they may be causal, not secondary, to the hypertension.
D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D004032:Diet; D004100:Dihydroxycholecalciferols / Q000097:blood; D004386:Duodenum / Q000033:anatomy & histology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007408:Intestinal Absorption; D008297:Male; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012964:Sodium / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*
D004100:Dihydroxycholecalciferols; D014807:Vitamin D; D012964:Sodium; D002118:Calcium