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

PF Pratt, S Bonnet, LM Ludwig, P Bonnet… - Hypertension, 2002 - Am Heart Assoc
PF Pratt, S Bonnet, LM Ludwig, P Bonnet, NJ Rusch
Hypertension, 2002Am Heart Assoc
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
α1C 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 …
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 α1C 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 α1C 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 α1C 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 α1C 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 α1C 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 α1C 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.
Am Heart Assoc