title: Intracellular angiotensin II increases the total potassium current and the resting potential of arterial myocytes from vascular resistance vessels of the rat. Physiological and pathological implications.
abstract: The influence of intracellular and extracellular administration of angiotensin II (Ang II; 10(-9) M) on total potassium current of arterial myocytes isolated from mesenteric arteries of Sprague Dawley rats was investigated. Measurements of total potassium current were performed using the voltage clamp whole cell configuration while the effect of intracellular Ang II on the resting potential of arterial myocytes was measured using the current clamp configuration of pCLAMP. The results indicated that: 1) intracellular Ang II (10(-9) M) increased the total potassium current by 73% ± 2.6% (n = 22; P < .05) within 5 minutes; 2) concurrently with the increment of potassium current, the resting potential was increased by 7 ± 1.5 mV (n = 23; P < .05); 3) extracellular administration of Ang II (10(-9) M) reduced the total potassium current by 20% ± 1.6% (n = 21; P < .05) within 5 minutes and depolarized the smooth muscle cells by 9 ± 2.3 mV (n = 26; P < .05); 4) the effects of intracellular Ang II on potassium current and membrane potential were inhibited by dialyzing a PKA inhibitor (10(-9) M) inside the cell together with Ang II (10(-9) M; P > .05); 5) valsartan (10(-9) M) dialyzed into the cell together with Ang II (10(-9) M) abolished the effect of the peptide on potassium current and membrane potential. The presence of endogenous or internalized intracellular Ang II in vascular resistance vessels and its effect on potassium current and resting potential indicates that the peptide present inside the arterial myocytes plays an important role on the regulation of vascular tone and consequently on peripheral resistance, which is a determining factor in the regulation of arterial blood pressure.
authors.affiliation: School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico 00936, USA. walmor.de-mello@upr.edu
authors.forename: Walmor C
authors.initials: WC
authors.lastname: De Mello
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects*; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D015221:Potassium Channels; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine