Published Online
on November 4, 2002

A more recent version of this article appeared on December 1, 2002

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Submitted on June 7, 2002
Revised on July 9, 2002

Increase in Cx45 Gap Junction Channels in Cerebral Smooth Muscle Cells from SHR

Xing Li and J. Marc Simard^*

From the Departments of Neurosurgery (X.L., J.M.S.), Pathology (X.L., J.M.S.), and Physiology (J.M.S.), University of Maryland School of Medicine, Baltimore, Md.

^* To whom correspondence should be addressed. E-mail: msimard{at}surgery1.umaryland.edu.

Abstract—We recently reported the novel finding of expression and function of connexin45 (Cx45) in cerebrovascular smooth muscle cells. We examined the hypothesis that Cx45 is altered in hypertension. Immunoblots for Cx45 showed a significant increase in Cx45 in cerebral arteries from adult spontaneously hypertensive rats (SHR) compared with adult Wistar-Kyoto (WKY) rats, with no difference in aorta or femoral artery. Patch-clamp of cerebral smooth muscle cells pairs from SHR versus WKY showed a significantly steeper voltage dependence of deactivation and partial block of junctional currents by quinine and by a peptide that interferes with docking of Cx45, consistent with dominance of functional Cx45 channels in SHR. We examined potential roles of blood pressure versus angiotensin in elevated Cx45 in SHR by measuring Cx45 protein in 4 groups: (1) long-term administration in Wistar rats of the nitric oxide synthase inhibitor L-NAME; (2) long-term administration in SHR of the ACE inhibitor captopril; (3) long-term administration in Wistar rats of angiotensin; and (4) exposure of basilar artery segments in organ culture to angiotensin. Blood pressure was significantly elevated in groups 1 and 3 and was normal in group 2. In groups 1, 2, and 4, there was no significant change in Cx45 protein. In group 3, there was a modest but insignificant increase in Cx45 protein but no change in voltage dependence of deactivation of junctional currents. Overall, our data show increased Cx45 in SHR that is unlikely to be due to either elevated blood pressure or to angiotensin. Relative dominance of Cx45 over Cx43 in cerebral vessels may predispose SHR to ischemic stroke.

Key words: hypertension, experimental • angiotensin II • ion channels • muscle, smooth vascular • stroke

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