POTASSIUM CHANNEL ANTAGONISTS AND VASCULAR REACTIVITY IN STROKE-PRONESPONTANEOUSLY HYPERTENSIVE RATS

The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular sm ooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of caro tid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractil e responses to tetraethylammonium (10(-4) to 3 X 10(-2) mol/L) and bar ium (3 X 10(-5) mol/L), blockers of the voltage-dependent and large co nductance, calcium activated potassium channels, were greater in carot id arteries from SHRSP than in those from WKY. In contrast, contractil e responses to the voltage-dependent potassium channel blockers 3,4-di aminopyridine (10(-6) to 3 X 10(-3) mol/L) and sparteine (10(-6) to 3 X 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9 ) to 10(-6) mol/L), an antagonist of the small conductance, calcium ac tivated potassium channel. Furthermore, relaxation responses to diazox ide (3 X 10(-4) mol/L), an activator of the ATP-sensitive potassium ch annel, and subsequent contractions to the ATP-sensitive potassium chan nel blocker glyburide (10(-8) to 3 X 10(-6) mol/L) in arteries from SH RSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large co nductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP.