Why the study?
Previous studies suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system, prompting investigation into whether it was mediated via the kinin-kallikrein system.
Does captopril and icatibant improve bone health in castrated hypertensive rats?
Does captopril and icatibant improve bone health in castrated hypertensive rats?
In a rat model of hypertension and osteoporosis, ACE inhibition with captopril decreased bone deterioration, an effect further enhanced by bradykinin receptor blockade.
Answers are grounded in this paper and cite their sources.
ACEI bone protection may involve KKS in hypertensive rat models; leaves open relevance to human osteoporosis or fracture risk.
Background. In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. Methods. Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. Results. Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats ([Formula: see text]). After castration, captopril decreased serum Ang II concentration ([Formula: see text]); in female rats, icatibant increased serum Ang II concentration ([Formula: see text]). Captopril increased serum bradykinin concentration ([Formula: see text]); in male rats, icatibant decreased serum bradykinin concentration ([Formula: see text]). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration ([Formula: see text]). Icatibant decreased urine DPD/Cr in male rats ([Formula: see text]) and increased osteocalcin concentration in female rats ([Formula: see text]). Captopril increased cancellous BMD in castrated hypertensive rats ([Formula: see text]), and icatibant further increased cancellous BMD ([Formula: see text]), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength ([Formula: see text]), and icatibant further improved it ([Formula: see text]). Conclusion. ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.
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Zhang et al. (2022) studied this question.
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