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Renal expression and function of oat1 and oat3 in rats with vascular calcification
Romina Bulacio1, María Herminia Hazelhoff, Adriana Mónica Torres
1Area Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, Universidad Nacional de Rosario, Rosario, Argentina.
Background/Aims:
Calcium overload in vascular smooth muscle is a highly pathogenic event, which progresses with advancing age. Old patients are polymedicated, and several pharmacotherapeutic agents circulate in the plasma as organic anions. The organic anion transporters 1 and 3 (Oat1 and Oat3) are present in renal basolateral membranes, which transport organic anions of pharmacological and physiological interest. This study was designed to evaluate the renal expression and function of Oat1 and Oat3 in rats with vascular calcification.
Methods:
Vascular calcification was induced by administration of a single dose of vitamin D(3) (300,000 UI/ kg b.w., i.m.) to male Wistar rats 10 days before the experiments. Oat1 and Oat3 expression was assessed by immunoblotting, immunohistochemistry and reverse-transcriptase polymerase chain reaction. The renal clearance of p-aminohippurate (PAH, a prototypical organic anion, substrate of Oat1 and Oat3) was measured by conventional clearance techniques.
Results:
Oat1 and Oat3 protein levels showed an increase in plasma membranes of renal proximal tubules of treated animals, where both transporters are functional. This could explain the increase observed in the renal clearance of PAH in treated rats.
Conclusions:
These results suggest the relevance of considering the existence of vascular calcification, which is common in ageing, when organic anion drugs are prescribed.
Insights
Vascular calcification increases renal organic anion transporters 1 and 3 (Oat1 and Oat3) expression and function. This impacts how the body processes organic anion drugs, especially in older patients.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Biology
Background:
- Vascular calcification is a common, pathogenic event in aging, affecting polymedicated older patients.
- Many circulating drugs are organic anions, requiring transport by specific renal transporters.
- Organic anion transporters 1 and 3 (Oat1 and Oat3) are key in renal organic anion transport.
Purpose of the Study:
- To investigate the renal expression and function of Oat1 and Oat3 in rats with induced vascular calcification.
- To understand how vascular calcification influences the handling of organic anion drugs.
Main Methods:
- Vascular calcification induced in male Wistar rats using a high dose of vitamin D3.
- Oat1 and Oat3 expression analyzed via immunoblotting, immunohistochemistry, and RT-PCR.
- Renal clearance of p-aminohippurate (PAH), an organic anion substrate, was measured.
Main Results:
- Increased protein levels of Oat1 and Oat3 were observed in the plasma membranes of renal proximal tubules.
- Both Oat1 and Oat3 transporters demonstrated functional activity in the treated rats.
- A significant increase in renal clearance of PAH was noted in rats with vascular calcification.
Conclusions:
- Vascular calcification enhances renal Oat1 and Oat3 expression and function.
- These changes can alter the pharmacokinetics of organic anion drugs.
- Clinical consideration of vascular calcification is crucial when prescribing organic anion medications, particularly for aging populations.
