Angiotensin (1-7) increases the potassium current and the resting potential of arterial myocytes from vascular resistance vessels of normal adult rats: Pathophysiological implications.
The influence of angiotensin (Ang) (1-7) on potassium current (Kv) and resting potential of smooth muscle cells isolated from mesenteric artery of Sprague Dawley rats was investigated. Measurements of potassium current were performed using the whole cell configuration of pCLAMP. The results indicated that Ang (1-7) (10(-9) M) increased the potassium current by 120% ± 2.6% (P < .05) and the resting potential of smooth muscle cells by 8 ± 2.8 mV (n = 23; P < .05). Ang II (10(-9) M) administered to the bath reduced the potassium current by 35% ± 3.6% (n = 23; P < .05) and depolarized the arterial myocytes by 7.8 ± 2.1 mV (n = 25; P < .05). The effect of the heptapeptide on potassium current was inhibited by a Mas receptor inhibitor (A779; 10(-8) M) as well as by a protein kinase A (PKA) inhibitor (10(-9) M) dialyzed into the cell. Intracellular dialysis of the catalytic subunit of PKA (5 × 10(-8) M) enhanced the potassium current by 38% ± 3.4% (n = 14; P < .05) but did not abolish the effect of Ang (1-7). On the other hand, Bis-1 (10(-9) M), which is a specific inhibitor of PKC, suppressed the effect of Ang (1-7) on potassium current. In conclusion, Ang (1-7) counteracts the effect of Ang II on potassium current and membrane potential of smooth muscle cells from mesenteric arteries, which are resistance vessels involved in the regulation of peripheral resistance and blood pressure. The activation of the cAMP/PKA cascade is essential for the effect of the heptapeptide. Pathophysiological implications are discussed.
School of Medicine, Medical Sciences Campus, UPR, San Juan, PR 00936-5067, USA. Electronic address: walmor.de-mello@upr.edu.
Walmor C
WC
De Mello
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008638:Mesenteric Arteries; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects
D010446:Peptide Fragments; D015221:Potassium Channels; D000803:Angiotensin I; C118790:angiotensin I (1-7)
Angiotensin (1-7); mesenteric artery; potassium current; rat; resting potential