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

An increased Ca influx attributed to dihydropyridine-sensitive L-type Ca 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 Ca 2 channel underlies this ionic defect. With the use of mesenteric arcade arteries from 12to 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 Ca -dependent tone, suggesting a functional role for 1C subunit upregulation in vascular hyperreactivity. To determine if these Ca 2 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 Ca -dependent tone attributed to L-type Ca 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 Ca channel pores are associated with the generation of abnormal vascular tone. (Hypertension. 2002;40: 214-219.)