Nifedipine protects small intestine from cyclosporine-induced hemodynamic and functional impairment
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S Sun1, S M Greenstein, D Y Kim
1Department of Surgery, Montefiore Medical Center, Bronx, New York 10467, USA.
Abstract:
We have previously shown that cyclosporine (CsA) causes intestinal hemodynamic and functional impairments. In this study, we evaluated whether nifedipine protects the small intestine from such toxic side effects. Isogeneic small intestinal transplantation was performed in rats which then received one of the following two-week treatments: olive oil, 0.15 ml/kg/day i.m. as vehicle controls in group 1; nifedipine, 1 mg/kg/day i.m. in group 2; CsA, 15 mg/kg/day i.m. in group 3; and both nifedipine and CsA in group 4. Vascular resistance, whole tissue blood flow and its mucosal and serosal/muscularis distributions in both graft and recipient residual native intestines, and absorptive function were determined. The data showed that two-week treatment with CsA resulted in a marked elevation of vascular resistance from 51.0 +/- 6.8 to 72.4 +/- 11.1 U/g in the native whole tissue and from 53.7 +/- 7.2 to 78.2 +/- 12.1 U/g in the graft whole tissue, and decreases in blood flow from 1.59 +/- 0.26 to 1.11 +/- 0.17 ml/g/min in the native whole tissue and from 1.50 +/- 0.21 to 1.03 +/- 0.18 ml/g/min in the graft whole tissue and absorption from 227 +/- 36 to 166 +/- 26 mg glucose/dl. Mucosa was preferentially affected, while serosal/muscularis layers remained relatively unchanged. When nifedipine was concomitantly used with CsA, vascular resistance and blood flow values in the mucosal layer and whole intestinal tissue as well as absorptive function showed no significant differences from the baseline data. The changes observed in denervated grafts and recipient native intestines were similar. We conclude that nifedipine is effective in protecting both graft and native small intestines from CsA-induced toxicity in the rat.
Insights
Nifedipine effectively protects the small intestine from cyclosporine (CsA) toxicity by maintaining normal blood flow and absorption. This study demonstrates nifedipine
Area of Science:
- Gastroenterology
- Pharmacology
- Transplantation Immunology
Background:
- Cyclosporine (CsA) is known to cause significant intestinal hemodynamic and functional impairments.
- Understanding the protective mechanisms against CsA-induced toxicity is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the protective effects of nifedipine against cyclosporine-induced toxicity in the small intestine.
- To assess the impact of nifedipine on intestinal hemodynamics, blood flow distribution, and absorptive function.
Main Methods:
- Isogeneic small intestinal transplantation in rats.
- Two-week treatment regimens: vehicle control, nifedipine alone, CsA alone, and combined nifedipine and CsA.
- Measurement of vascular resistance, blood flow (whole tissue, mucosal, serosal/muscularis), and absorptive function.
Main Results:
- CsA treatment significantly increased vascular resistance and decreased blood flow and absorption in both native and grafted intestines.
- CsA preferentially affected the mucosal layer, with serosal/muscularis layers remaining relatively unchanged.
- Concomitant nifedipine administration with CsA prevented these adverse effects, maintaining baseline vascular resistance, blood flow, and absorptive function.
Conclusions:
- Nifedipine effectively protects both native and transplanted small intestines from CsA-induced toxicity.
- Nifedipine preserves intestinal hemodynamic and functional integrity when co-administered with CsA.
- These findings suggest a potential therapeutic role for nifedipine in mitigating CsA-related gastrointestinal complications.