leiurotoxin-i and Hypertension

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)

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Age Factors; Animals; Apamin; Calcium; Calcium Channel Blockers; Calcium Channels; Charybdotoxin; Femoral Artery; Hypertension; Ion Channel Gating; Male; Membrane Potentials; Muscle, Smooth, Vascular; Nifedipine; Peptides; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Scorpion Venoms; Verapamil