Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats.
We examined whether the Ca2+ channel function in the resting state alters the resting tone in femoral and carotid arteries from spontaneously hypertensive rats (SHR) at early hypertensive stages (6 and 4 weeks of age), and data were compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). Strips of femoral and carotid arteries from 6-week-old SHR, but not from WKY, maintained a myogenic tone, that is, the resting tone decreased when 10(-7) M nifedipine was added. A similar myogenic tone was maintained in 4-week-old SHR. In strips of carotid arteries preloaded with fura-2, a fluorescent Ca2+ indicator, the decrease in cytoplasmic Ca2+ concentration following 0-Ca2+ solution or 5 x 10(-7) M nicardipine was significantly greater in SHR than in WKY. The basal 45Ca influx in femoral and carotid arteries from 6-week-old SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by 10(-7) M nifedipine. The addition of charybdotoxin (a blocker of large conductance Ca(2+)-activated K+ channels) or of Bay k 8644 (an agonist of L-type voltage-dependent Ca2+ channels; VDCs), caused a concentration-dependent contraction, which was significantly greater in 6- and 4-week-old SHR than in WKY. These results suggest that the Ca2+ influx via L-type VDCs was increased in the resting state of femoral and carotid arteries from SHR at the early hypertensive stages, and therefore the myogenic tone was maintained and charybdotoxin-sensitive K+ channels were highly activated.
Asano
M
M
Department of Pharmacology, Nagoya City University Medical School, Japan.
Matsuda
T
T
Hayakawa
M
M
Ito
K M
KM
Ito
K
K
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D018999:Charybdotoxin; D004594:Electrophysiology; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology
D002132:Calcium Radioisotopes; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2