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(Hypertension. 2002;40:214.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Upregulation of L-Type Ca²⁺ Channels in Mesenteric and Skeletal Arteries of SHR

Phillip F. Pratt; Sebastien Bonnet; Lynda M. Ludwig; Pierre Bonnet; Nancy J. Rusch

From the Department of Pharmacology and Toxicology, Medical College of Wisconsin (P.F.P., L.M.L., N.J.R.), Milwaukee; Laboratoire de Physiologie Cellulaire Respiratoire, INSERM 9937, Universite Bordeaux 2 (S.B.), Bordeaux, France; and Laboratoire de Physiopathologie de la paroie Arterielle, Faculty of Medicine (P.B.), Tours, France.

Correspondence to Dr Nancy J. Rusch, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail nrusch{at}mcw.edu

An increased Ca²⁺ influx attributed to dihydropyridine-sensitive L-type Ca²⁺ channels has been demonstrated in mesenteric vascular smooth muscle cells of spontaneously hypertensive rats (SHR). This study examined whether an upregulation of the pore-forming _1C subunit of the L-type Ca²⁺ channel underlies this ionic defect. With the use of mesenteric arcade arteries from 12- to 16-week-old SHR and normotensive Wistar Kyoto (WKY) rats, reverse transcriptase–polymerase chain reaction demonstrated an increased level of amplified cDNA corresponding to the _1C subunit mRNA in the SHR arteries. Western blots confirmed that the increased mRNA expression was associated with a 3.4-fold increase in the immunoreactive signal of the _1C subunit protein in SHR compared with WKY mesenteric arteries, and immunocytochemistry confirmed this abnormality at the single-cell level. Finally, isolated mesenteric arteries from SHR were highly reactive to Bay K8644 and developed anomalous Ca²⁺-dependent tone, suggesting a functional role for _1C subunit upregulation in vascular hyperreactivity. To determine if these Ca²⁺ channel abnormalities extended to the SHR skeletal muscle bed, we repeated a similar series of studies in WKY and SHR hind limb arteries. Skeletal muscle arteries from SHR also expressed higher levels of _1C subunit mRNA and protein than WKY arteries and developed anomalous Ca²⁺-dependent tone attributed to L-type Ca²⁺ channels. Our data provide the first evidence that the _1C subunit mRNA and protein are upregulated in SHR arteries and that the increased numbers of L-type Ca²⁺ channel pores are associated with the generation of abnormal vascular tone.

Key Words: calcium channels • muscle, smooth, vascular • arteries • mesenteric arteries • rats, spontaneously hypertensive • hypertension, arterial

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