Increased function of voltage-dependent Ca++ channels and Ca(++)-activated K+ channels in resting state of femoral arteries from spontaneously hypertensive rats at prehypertensive stage.
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)
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D005263:Femoral Artery / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; C056574:leiurotoxin I; D001030:Apamin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium