Salt-sensitive hypertension induces renal injury via decreased blood flow in the renal artery (RA), and ion channel dysfunction in RA myocytes (RAMs) may be involved in the higher renal vascular resistance. We examined the effects of several voltage-gated K (K V ) channel blockers on the resting tension in endothelium-denuded RA strips and delayed-rectifier K currents in RAMs of Dahl salt-sensitive hypertensive rats (Dahl-S) fed with low-(Dahl-LS) and high-salt diets (Dahl-HS). The tetraethylammonium (TEA)-induced contraction in RA strips were significantly larger in Dahl-HS than Dahl-LS. Correspondingly, TEA-sensitive K V currents were significantly larger in the RAMs of Dahl-HS than Dahl-LS. Among the TEA-sensitive K V channel subtypes, the expression levels of K V 2.1 transcript and protein were significantly higher in the RA of Dahl-HS than Dahl-LS, while those of K V 1.5, K V 7.1, and K V 7.4 transcripts was comparable in two groups. K V 2.1 currents detected as the guangxitoxin-1E-sensitive component were larger in the RAMs of Dahl-HS than Dahl-LS. These suggest that the up-regulation of the K V 2.1 channel in RAMs may be involved in the compensatory mechanisms against decreased renal blood flow in salt-sensitive hypertension.
Key words voltage-gated K+ (K V ) channel; K V 2.1; salt-sensitive hypertension; Dahl rat; renal artery K + channels play key roles in the regulation of the membrane excitability of vascular smooth muscle (VSM). 1,2) A number of studies support there being important roles for voltage-gated (K V ), delayed-rectifier K + channels in the regulation of the resting membrane potential in VSM. 2-4) The molecular diversity of delayed-rectifier K V channel subtypes is fundamental to an understanding of the differences in membrane excitability and the regulation of vascular tone. The molecular components of the delayed-rectifier K V channels have been identified in VSMs: K V 1.x and K V 2.x. 5-7) K V 1.x and K V 2.x superfamily members have been implicated in the inhibition of myogenic tension in resistant arteries. [7][8][9][10][11] The expression of the K V 1.5 transcripts has been shown to be decreased in the pulmonary artery in pulmonary hypertension.12) The loss of K V 1.5 and K V 2.1 expression stimulates cell proliferation and inhibits apoptosis in pulmonary arterial myocytes in pulmonary hypertension model rats.13) Moreover, the K V channel encoded by K V 2.1 was reduced in cerebral arterial myocytes from angiotensin II-induced hypertensive rats. 9) These show that the loss of K V channel function is responsible for the development of hypertension. On the other hand, an increase in K + channel function represents a compensatory reaction in an effort to limit the development of hypertension. In the small mesenteric artery of spontaneously hypertensive rat (SHR), an animal model of primary hypertension, the K V channel function encoded by K V 1.2, K V 1.5, and K V 2.1 was significantly enhanced compared with normotensive rats. 14,15) Thus, an understanding of the modification of K V chan...