Oral Calcium Supplements With L ‐Proline and Sodium Zinc Chlorophyllin Preserve Elevated Transepithelial Calcium Transport in Spontaneously Hypertensive Rats

ABSTRACT

Hypertensive rodents often exhibit bone loss and osteopenia with impaired bone formation. We hypothesized that spontaneously hypertensive rats (SHR) could compensate for osteopathy through certain mechanisms, particularly intestinal calcium absorption. However, this calcium transport may be suppressed after long‐term exposure to high luminal calcium levels during calcium supplementation through a molecular mechanism known as calcium‐dependent inactivation of calcium channels. Herein, we designed calcium‐rich formulations—that is, 14 mM CaCl ₂  + 12 mM

‐Proline +20 µM sodium zinc chlorophyllin (CaA) and 14 mM CaCl ₂  + 12 mM ‐Proline +60 µM sodium zinc chlorophyllin (CaB), with a total elemental calcium amount of < 16 mg/kg/day—administered orally to SHR and wild‐type rats (WT), aiming to avoid suppressing the calcium transport rate. We found that SHR had greater systolic, diastolic, and mean arterial pressures than WT, while both CaA and CaB did not alter these parameters. Using an Ussing chamber with ⁴⁵ Ca radioactive tracer, both regimens did not affect the enhanced transepithelial calcium transport in the duodenum of SHR, although they increased epithelial potential difference and short‐circuit current, indicators of electrogenic ion fluxes. Meanwhile, they did not alter mRNA expression levels of calcium transporters or tight junction components in the mucosal cells. In conclusion, unlike the known suppressive effects of certain calcium compounds on calcium absorption, oral administration using CaA and CaB formulations maintained high transport rates in SHR. This finding helps provide a basis for further clinical investigation into the optimization of calcium supplementation, particularly in the context of hypertension and osteoporosis.