Enhancement of receptor-operated cation current and TRPC6 expression in arterial smooth muscle cells of deoxycorticosterone acetate-salt hypertensive rats

• Published in: Journal of hypertension Vol. 25; no. 4; pp. 809 - 817
• Main Authors: YOUNG MIN BAE, KIM, Aeran, SUNG IL CHO, KIM, Duk-Kyung, HO, Won-Kyung, YOUNG JOO LEE, LIM, Wonchung, NOH, Yun-Hee, KIM, Eun-Ju, KIM, Junghwan, KIM, Tae-Kyung, SANG WOONG PARK, KIM, Bokyung
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-04-2007
• Subjects: Aldosterone - pharmacology; Animals; Aorta - cytology; Arterial hypertension. Arterial hypotension; Arteries - cytology; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood vessels and receptors; Blotting, Western; Calcium Channels - biosynthesis; Calcium Channels - drug effects; Cardiology. Vascular system; Desoxycorticosterone; Disease Models, Animal; Experimental diseases; Fundamental and applied biological sciences. Psychology; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - physiopathology; Medical sciences; Mesenteric Artery, Superior - cytology; Muscle, Smooth, Vascular - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Norepinephrine - pharmacology; Potassium Channels, Calcium-Activated - drug effects; Potassium Channels, Calcium-Activated - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Serotonin - pharmacology; Serotonin Agents - pharmacology; TRPC Cation Channels - biosynthesis; TRPC Cation Channels - drug effects; Up-Regulation - drug effects; Vasoconstrictor Agents - pharmacology; Vertebrates: cardiovascular system; Hypertension; vascular smooth muscle; Rat; Steroid hormone; Mineralocorticoid; Rodentia; Cardiovascular disease; Smooth muscle; transient receptor potential channels; Aldosterone; Vertebrata; Mammalia; Animal; Adrenal hormone; cation channels
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/hjh.0b013e3280148312

In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, altered reactivity of blood vessels to vasoactive agonists is frequently associated with an elevation in blood pressure. Canonical transient receptor potential (TRPC) channels are believed to encode receptor-operated cation channels (ROC), the activation of which is involved in smooth muscle depolarization and vasoconstriction. The aims of the present study were to investigate whether the ROC current is increased in DOCA-hypertensive rats and determine whether aldosterone directly enhances the expression of TRPC.
The nystatin-perforated patch-clamp technique was used for the recording of receptor-stimulated ion currents in mesenteric arterial smooth muscle cells, which were enzymatically dispersed from sham-operated and DOCA-salt hypertensive rats. Expressions of TRPCs were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Western blot analysis.
Receptor-stimulated currents activated by 5-hydroxytryptamine (serotonin) and norepinephrine were increased significantly in the mesenteric arterial smooth muscle cells of DOCA-salt hypertensive rats compared to sham-operated rats. Ion-substitution experiments revealed that the enhanced currents were cation currents (ROC currents). Enhanced expression of TRPC6 in mesenteric arteries from DOCA-salt hypertensive rats was demonstrated by real-time RT-PCR. Up-regulation of TRPC6 by aldosterone treatment in vitro was also observed in A7r5 cells by RT-PCR and in western blots.
These results suggest that aldosterone enhances TRPC6 expression and ROC currents in vascular smooth muscle cells, and that this may in turn contribute to altered vascular reactivity and to hypertension.