Mechanical stretch reduces the effect of angiotensin II on potassium current in cardiac ventricular cells of adult Sprague Dawley rats. On the role of AT1 receptors as mechanosensors.
The influence of mechanical stretch on the effect of angiotensin II (Ang II) on potassium current was investigated on cardiomyocytes isolated from the left ventricle of adult Sprague Dawley rats. Measurements of total potassium current were performed using the voltage clamp whole cell configuration. The results indicated: that mechanical stretch increased the potassium current appreciably, an effect inhibited by valsartan (10(-8) M), which is a strong inverse agonist of AT1 receptors; Ang II (10(-8) M) administered to the bath increased the potassium current by 60 ± 5.2% (n = 22) in cardiomyocytes isolated from Sprague Dawley rats; mechanical stretch (3 μm) applied in the longitudinal direction for a duration of 10 minutes, reduced the effect of Ang II (10(-8) M) on potassium current to 25 ± 4.3% (n = 24); 4) Bis-1 (300 nM), which is a specific inhibitor of protein kinase C, inhibited the effect of mechanical stretch on the increment of potassium current elicited by Ang II. In conclusion, the mechanical stretch of cardiomyocytes increases the potassium currents, an effect greatly dependent on the mechanical activation of AT1 receptors independently of Ang II. In addition, the increment of potassium currents caused by Ang II was greatly reduced by mechanical stretch, an effect abolished by protein kinase C inhibition.
School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR. walmor.de-mello@upr.edu
Walmor C
WC
De Mello
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D007211:Indoles; D008301:Maleimides; D015221:Potassium Channels; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000068756:Valsartan; D011493:Protein Kinase C; D014633:Valine; C070515:bisindolylmaleimide I