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Real-time Evaluation of Absolute, Cytosolic, Free Ca2+ and Corresponding Contractility in Isolated, Pressurized Lymph Vessels
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Cyclosporine A impairs norepinephrine-induced vascular contractility
Tobias Bergler1, Markus Resch, Stephan W Reinhold
1Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany. tobias.bergler @ klinik.uni-regensburg.de
Kidney & Blood Pressure Research
|October 26, 2012
Summary
Cyclosporine A (CsA) impairs kidney function by reducing mesenteric adrenoreceptors, leading to blunted vascular responses to norepinephrine. Everolimus did not show these effects.
Area of Science:
- Nephrology
- Pharmacology
- Vascular Biology
Background:
- Cyclosporine A (CsA) use post-kidney transplant is linked to nephrotoxicity and vasculopathy.
- Mechanisms of CsA-induced vascular dysfunction require further investigation.
Purpose of the Study:
- To investigate the effects of CsA on vascular contractility and adrenoreceptor expression in a rat kidney transplant model.
- To compare CsA's effects with everolimus and assess impacts on mesenteric resistance arteries versus the thoracic aorta.
Main Methods:
- Utilized a rat kidney transplantation model with pressurized myography to assess vascular contractility.
- Correlated functional data with mRNA expression studies of α- and β-adrenoreceptors.
- Administered CsA and everolimus to evaluate their specific impacts.
Main Results:
- CsA significantly downregulated mesenteric adrenoreceptor mRNA expression, with no effect on aortic adrenoreceptors.
- Mesenteric resistance arteries showed reduced contractile responses to norepinephrine after CsA treatment.
- Endothelin-induced contractions and everolimus treatment did not affect contractility or adrenoreceptor expression.
Conclusions:
- CsA treatment blunts norepinephrine-induced, but not endothelin-induced, contractility in mesenteric resistance arteries.
- This functional change is associated with marked adrenoreceptor downregulation in mesenteric arteries, specific to CsA use.
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