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M Asano, Y Nomura, K Ito, Y Uyama, Y Imaizumi and M Watanabe
Department of Pharmacology, Nagoya City University Medical School, Japan.
The present study examined the possible role of voltage-dependent Ca++ channels (VDCs) and Ca(++)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR) at a prehypertensive stage. Differences in the effects of agents that interact with these channels were assessed in endothelium- denuded strips of femoral arteries isolated from 4-week-old SHR and age- matched normotensive Wistar-Kyoto rats (WKY). Systolic blood pressures at this age were not significantly different between SHR and WKY. The arterial strips from SHR maintained a myogenic tone in the resting state; that is the resting tone in the SHR artery was abolished when either the bathing solution was replaced with a Ca(++)-free solution or 10(-7) M nifedipine was added. Studies using 1- or 5-min pulse labeling of the arteries with 45Ca showed that the resting Ca++ influx was significantly increased in SHR when compared with WKY, and this increase in SHR was abolished by 10(-7) M nifedipine. In strips preloaded with fura-PE3, the addition of 3 x 10(-6) M verapamil to resting muscles decreased the resting cytosolic Ca++ level and caused a relaxation. These effects of verapamil were more evident in SHR than in WKY. The addition to the strips of charybdotoxin and iberiotoxin, blockers of large conductance KCa channels, caused a concentration- dependent contraction, which was significantly greater in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
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