Antihypertensive and arterial anticalcinotic effects of calcium antagonists

Fleckenstein, A.; Frey, M.; Fleckenstein-Grün, G.

doi:10.1016/0002-9149(86)90798-8

Cited by 63 publications

(19 citation statements)

References 6 publications

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“…The aim of the present study was to evaluate the renal expression and function of Oat1 and Oat3 in an experimental model of vascular calcium overload induced in male Wistar rats with an overdose of vitamin D 3 . The renal expression of both Oat1 and Oat3 was assessed using immunoblotting and immunohistochemical techniques (light-microscopic and confocal immunofluorescence-microscopic analysis) for protein expression and reverse-transcriptase polymerase chain reaction (RT-PCR) for mRNA expression, while their function was evaluated by measuring PAH renal elimination with conventional clearance techniques.…”

Section: Oat1 and Oat3 Expression In Vascular Calcificationmentioning

confidence: 99%

Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Bulacio¹,

Hazelhoff²,

Torres³

2012

Pharmacology

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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 D₃ (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.

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Section: Oat1 and Oat3 Expression In Vascular Calcificationmentioning

confidence: 99%

Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Bulacio¹,

Hazelhoff²,

Torres³

2012

Pharmacology

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“…The largest increase is noted in compliance vessels, such as the aorta, but marked increases also occur in small muscular arteries. It is clearly a continuously developing process that starts many years before cytotoxic degrees of calcium overload are reached 1,2 …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Quaglia

Hofer

Torres

2002

Clin Exp Pharmacol Physiol

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1. Ageing induces calcium accumulation in the vascular system. The simplest experimental way of producing high degrees of arterial calcium overload is by administration of an overdose of vitamin D(3) to rats. The aim of the present study was to evaluate the pharmacokinetics of organic anions in rats with arterial calcinosis induced by an overdose of vitamin D(3). 2. We used bromosulfophthalein (BSP) and sulfanilamide (SA) as models of organic anions with preferential biliary and renal excretion, respectively. 3. Increases in the clearance and elimination rate constant of BSP were observed in treated rats. The clearance and the elimination rate constant for SA were also increased in rats with arterial calcinosis. 4. Variations in arterial hepatic blood flow, aspartate aminotransferase activity and liver calcium accumulation were not observed in treated rats. In contrast, treated rats had a lower renal blood flow and increased renal calcium levels. 5. In summary, rats with arterial calcinosis showed an increase in total body clearance of both BSP and SA, probably associated with modifications in their metabolism and/or in organ extraction. Alterations to hepatic and renal blood flow do not account for these phenomena.

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“…Fleckenstein et al [15] carried out extensive experimental studies with various models of arterial calcinosis or arteriosclerosis in rats. The most interesting results were obtained in aging rats.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent increase in arterial smooth muscle calcium in spontaneously hypertensive rats

et al. 1988

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Alterations in cellular calcium metabolism in essential hypertensive and in the SHR have been described. In the present study, particle-induced X-ray emission (PIXE) was used to get some information on the spatial distribution of Ca2+ in aortas of spontaneously hypertensive rats (SHR) and normotensive controls aged 1 week, 4 weeks, and 12 weeks. It was found that the Ca2+ content was not elevated in the aortic smooth muscle of SHR aged 1 week (n = 9) as compared to normotensive controls (n = 8) (186.8 +/- 89.9 micrograms Ca2+/g tissue vs 254.0 +/- 73.7 micrograms Ca2+/g tissue. The Ca2+ content was significantly raised in the aortic smooth muscle of SHR aged 4 weeks (n = 9) as compared to 4-weeks-old WKY rats (n = 12) (726.0 +/- 130.4 Ca2+/g tissue vs 440.3 +/- 214.4 Ca2+ micrograms/g tissue and in SHR aged 3 months (n = 15) as compared to WKY rats (n = 12), respectively (3317.0 +/- 734.0 micrograms Ca2+/g tissue vs. 1632.0 +/- 569.6 micrograms Ca2+/g tissue). The results confirm the age-related increase in the arterial Ca2+ content in normotensive rats and demonstrate additionally that this age-related rise in arterial Ca2+ content is accelerated in SHR.

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Antihypertensive and arterial anticalcinotic effects of calcium antagonists

Cited by 63 publications

References 6 publications

Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Age-dependent increase in arterial smooth muscle calcium in spontaneously hypertensive rats

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