Remission of high blood pressure reverses arterial potassium channel alterations.
Rat arterial muscle cells show an elevated Ca(2+)-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) mol/L calcium to amplify Ca(2+)-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 Ca(2+)-dependent K+ channels by tetraethylammonium. Our findings imply that Ca(2+)-dependent K+ current density in arterial muscle membranes shows a positive correlation with chronic arterial blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Rusch
N J
NJ
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Runnells
A M
AM
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004594:Electrophysiology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D017257:Ramipril / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D017257:Ramipril