Abstract:
BACKGROUND/AIMS:Previous studies have shown that L-type Ca2+ channel (LCC) blockers prevent the afferent arteriolar (AA) vasoconstriction elicited by angiotensin II (Ang II), but do not influence its vasoconstrictor effect on efferent arterioles (EA). The present study tested the hypothesis that Ang II-mediated constriction of AA and EA involves T-type Ca2+ channel (TCC) activation, which may mediate Ca2+ entry responsible for Ang II-induced EA and possibly AA constriction. METHODS:Video-microscopic measurements of vascular dimensions were performed on isolated blood-perfused juxtamedullary nephrons from Sprague-Dawley rats. Single AA or EA were visualized and superfused with solutions containing Ang II alone or with a TCC blocker, pimozide, or a LCC blocker, diltiazem. RESULTS:Pimozide at 10 micromol/l significantly dilated EA (19.7 +/- 1.4%) as well as AA (24.8 +/- 3.6%). In response to superfusion with Ang II at concentrations of 0.1, 1.0 and 10.0 nmol/l, AA diameter decreased significantly by 15.2 +/- 1.7, 23.3 +/- 3.2 and 36.1 +/- 3.4% and EA diameter also decreased significantly by 11.9 +/- 1.7, 19.6 +/- 2.8 and 31.0 +/- 2.6%, respectively. Pimozide (10 micromol/l) markedly blunted AA (4.6 +/- 1.2, 7.5 +/- 0.6 and 7.9 +/- 1.2%) and EA (2.2 +/- 0.6, 5.4 +/- 1.5 and 7.7 +/- 1.3%) diameter responses to Ang II. Diltiazem (10 micromol/l) significantly dilated AA (26.8 +/- 2.2%), and prevented Ang II-mediated constriction of AA. In contrast, diltiazem did not dilate EA (3.3 +/- 0.6%) and failed to inhibit the Ang II-induced EA vasoconstriction; however, the vasoconstriction was reversed by the subsequent addition of pimozide (5 micromol/l). CONCLUSION:This study provides further functional evidence for TCC channels in the regulation of AA and EA indicating that Ang II-mediated arteriolar constriction may involve activation of TCC in both AA and EA. TCC may play an important role in mediating Ca2+ entry responsible for Ang-induced EA and AA constriction. The role of TCC in mediating Ang II-constrictor actions on EA may be of particular significance because LCC are not normally functional in these vessels.
journal_name
Am J Nephroljournal_title
American journal of nephrologyauthors
Feng MG,Navar LGdoi
10.1159/000082946subject
Has Abstractpub_date
2004-11-01 00:00:00pages
641-8issue
6eissn
0250-8095issn
1421-9670pii
82946journal_volume
24pub_type
杂志文章abstract:BACKGROUND:African Americans (AAs) suffer the widest gaps in chronic kidney disease (CKD) outcomes compared to Caucasian Americans (CAs) and this is because of the disparities that exist in both health and healthcare. In fact, the prevalence of CKD is 3.5 times higher in AAs compared to CAs. The disparities exist at al...
journal_title:American journal of nephrology
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-03-01 00:00:00
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更新日期:2020-01-01 00:00:00
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pub_type: 杂志文章,评审
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