Date of Award
Doctor of Philosophy
The purpose of this study was to evaluate the possible mechanisms involved in cremasteric arteriolar dilation as a result of increased concentrations of ([K+]o) extracellular potassium. Many other studies suggested that Na+/K+ ATPase or KIR channels are responsible for potassium-induced vasodilation in other systems (2, 12, 22, 40, 46, 52, 16, 17, 25, 33, 34, 85, 99, 151). However, these studies show only partial inhibition of dilation as a result of independent blockageof each mechanism. The hypothesis of this study was that both mechanisms contribute to potassium-induced dilation seen in cremasteric arterioles.
First or second order arterioles were isolated (n = 81), cannulated and pressurized with physiological salt solution (PSS) to 70 cm H2 O at 34°C with no flow through their lumens. The vessels developed spontaneous tone in PSS containing 5 mM K+ . Elevation of [K+] o from 5 mM to 8.75, 12.5 or 20 mM was studied to determine if K+ caused concentration-dependent dilation. Arteriolar diameter was measured using a computer-based diameter tracking system. To elucidate the mechanism(s) responsible for the dilation, vessels were exposed to known blockers of KIR and Na+/K+ ATPase. Barium (50 μM or 100 μM), which blocks KIR channels, was applied to vessels to determine if blockage of KIR channels would inhibit potassium-induced vasodilation. Ouabain (0.1 mM or 1.0 mM), an inhibitor of the Na+/K+ ATPase, was applied to vessels in order to determine if blockage of Na+/K+ ATPase would result in inhibition of potassium-induced vasodilation.
Increased [K+]o caused transient vasodilation. The arterioles dilated and then returned to, or below baseline despite the maintenance of the elevated [K+]o . Concentrations of barium (50 μM and 100 μM) (n = 8 for both concentrations p < 0.05) resulted in a reduction in the peak dilation to 20 mM K+ . Ouabain, 0.1 mM (n = 9, p < 0.05) or 1 mM (n = 14, p < 0.05), resulted in a reduction in the peak dilation to 20 mM K+. However, the dilation was not consistently eliminated by either blocker. A combination of barium (100 μM) and ouabain (1 mM) was required to dependably abolish K+ -induced arteriolar dilation.
The effects of both barium and ouabain appeared to be specific because dilation induced by acetylcholine was not inhibited by either agent.
These results suggest that skeletal muscle arterioles are intrinsically sensitive to changes in [K+]o, and that the transient nature of the response to elevated [K+]o is an innate property of the arteriolar muscle cells. Increases in [K+]o appear to dilate skeletal muscle arterioles by a mechanism that involves both KIR channels and the Na+/K+ ATPase.
Burns, Wendy, "K+- Induced Dilation of Cremasteric Arterioles Involves Na+/K+Atpase and Inward Rectifier K+ Channels" (2003). Dissertations. 1084.