Increased Ca2+ influx in the resting state maintains the myogenic tone and activates charybdotoxin-sensitive K+ channels in femoral arteries from young SHR

Abstract

1. To determine the possible role of voltage-dependent Ca2+ channels (VDCC) and Ca2+-activated K+ (KCa) channels in the regulation of resting tone of arteries from young spontaneously hypertensive rats (SHR), mechanical responses to the agents which interact with these channels were examined in endothelium-denuded strips of femoral arteries from 4 week old SHR and age-matched normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressures at this age were not significantly different between SHR and WKY. 2. The strips from SHR, but not from WKY, maintained a myogenic tone; that is, the resting tone decreased when nifedipine was added. 3. Studies using 1 or 5 min pulse labelling of the strips with 45Ca showed that the basal Ca2+ influx was increased in SHR when compared with WKY, and this increase in SHR was abolished by nifedipine. Similar results were obtained when the cytoplasmic Ca2+ concentration ([Ca2+]i) in the resting state of the strips was measured by fura-PE3. 4. The addition of charybdotoxin (ChTX, a blocker of large conductance KCa channels) to the resting state caused a concentration-dependent contraction, which was much greater in SHR than in WKY. The ChTX-induced contraction in SHR was abolished by nifedipine. 5. In strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in SHR than in WKY. The increase in 86Rb efflux in SHR was abolished by nifedipine. 6. The results suggest that the Ca2+ influx via L-type VDCC was increased in the resting state of the femoral artery from 4 week old SHR, and therefore the myogenic tone was maintained and ChTX-sensitive K+ channels were highly activated.