REMISSION OF HIGH BLOOD-PRESSURE REVERSES ARTERIAL POTASSIUM CHANNEL ALTERATIONS

Rat arterial muscle cells show an elevated Ca2+- dependent K+ efflux during the established phase of hypertension. This association of enhanced K+ efflux with high arterial pressure implies that changes of in vivo blood pressure can alter the level of K+ channel current in arterial membranes. We directly tested this hypothesis by comparing K+ current density between patch-clamped aortic muscle membranes of normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with the angiotensin-converting enzyme inhibitor ramipril (3.5 mg/kg per day PO) to normalize blood pressure. Peak macroscopic K+ current was measured during progressive depolarizing steps (10 mV) from -60 and +60 mV in cells dialyzed with pipette solution containing 10(-6) moI/L calcium to amplify Ca2+-dependent K+ current. With the use of this approach, maximum K+ current density in aortic muscle membranes of untreated SHR was 2.6-fold higher than in untreated WKY rats (SHR, 31+/-3 pA/pF; WKY, 12+/-1 pA/pF) and was predominantly blocked by 2 mmol/L tetraethylammonium. K+ current density in SHR aortic membranes was unchanged after 1 week of ramipril therapy, but it was reduced 42% (to 18+/-1 pA/pF) after 2 weeks of treatment. Parallel tension-recording studies showed that untreated SHR aortic segments but not aortic segments from WKY rats or ramipril-treated SHR constricted strongly after block of Ca2+-dependent K+ channels by tetraethylammonium. Our findings imply that Ca2+-dependent K+ current density in arterial muscle membranes shows a positive correlation with chronic arterial blood pressure levels. The enhanced expression of this K+ current in arterial membranes of hypertensive animals may be a homeostatic mechanism to regulate vascular excitability and hence prevent further arterial contraction during this disease.