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β1 adrenergic receptor‐initiated dilation in rat cerebral arteries is mediated by Shaker ‐type K V 1 channels and is attenuated in angiotensin II‐induced hypertension
Author(s) -
Joseph Biny K,
Rusch Nancy J,
Rhee Sung W
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.932.14
Subject(s) - cerebral arteries , vasodilation , medicine , endocrinology , cerebral circulation , angiotensin ii , dilator , renin–angiotensin system , adrenergic , chemistry , receptor , blood pressure
The β1 adrenergic receptor (β1AR), a protein ubiquitously expressed in the cardiovascular system, initiates vasodilation in the cerebral circulation. For example, rat cerebral arteries dilate robustly to isoproterenol (ISO) and norepinephrine (NE), and these responses are blocked by atenolol, a β1AR blocker. However, the identity of the ion channel(s) that mediate the β1AR‐initiated dilation is unclear. In this study, we report that the dilator responses to ISO and NE of isolated, cannulated rat cerebral arteries perfused at 60 mm Hg are abolished by 1 μM correolide, a selective blocker of Shaker ‐type voltage‐gated (K V 1) channels. To examine the effect of hypertension on this dilation, we used Sprague‐Dawley rats subcutaneously infused with angiotensin II (Ang II, 500 ng/kg/min) for two weeks. Cerebral arteries from Ang II hypertensive rats dilated significantly less to ISO and NE compared to the saline‐infused control rats, suggesting a loss of β1AR‐initiated dilation. Real‐time PCR revealed a reduction in gene expression of pore‐forming α1.2 and α1.5 subunits of K V 1 channels in cerebral arteries of Ang II hypertensive rats. Collectively, our study provides evidence for: i) a functional coupling of K V 1 channels and β1AR in rat cerebral arteries, and ii) a coordinated loss of this vasodilator pathway in the Ang II rat model of hypertension that may result in cerebral blood flow abnormalities. AHA 0715570Z (BKJ)