Possible mechanism of the potent vasoconstrictor responses to ryanodine in dog cerebral arteries.
Isolated cerebral (basilar, posterior communicating and middle cerebral) arteries exist in a partially contracted state. To determine the Ca(2+)-buffering function of sarcoplasmic reticulum in the resting state of cerebral arteries, the effects of ryanodine that eliminates the function of sarcoplasmic reticulum, on tension and cellular Ca2+ level were compared in endothelium-denuded strips of the cerebral, coronary and mesenteric arteries of the dog. The addition of ryanodine to strips with basal tone caused a concentration-dependent contraction, which was significantly greater in the cerebral arteries than in the mesenteric or coronary artery. In the presence of 10(-5) M ryanodine, the caffeine (20 mM)-induced contraction was greatly attenuated in these arteries. After washout, the basal tone was greatly elevated in the cerebral arteries. The elevated tone was abolished by 10(-7) M nifedipine. The ryanodine-induced contractions were also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the basal tone in the cerebral arteries, suggesting the maintenance of myogenic tone. The basal Ca2+ influx in arteries measured after a 5-min incubation with 45Ca was significantly higher in the basilar artery than in the mesenteric artery. The basal Ca2+ influx was not increased by 10(-5) M ryanodine in either artery. The basal Ca2+ influx was decreased by 10(-7) M nifedipine in the basilar artery, but was unchanged in the mesenteric artery. These results suggest that: (1) the basal Ca2+ influx via L-type voltage-dependent Ca2+ channels was higher in the resting state of the cerebral arteries; (2) the greater part of the higher Ca2+ influx was buffered by Ca2+ uptake into the sarcoplasmic reticulum; and (3) therefore the functional elimination of sarcoplasmic reticulum by ryanodine caused a potent contraction in these arteries. Furthermore, the maintenance of myogenic tone in the cerebral arteries suggests that more Ca2+ enters the smooth muscle cell than the buffering ability of sarcoplasmic reticulum can handle.
Asano
M
M
Department of Pharmacology, Nagoya City University Medical School, Japan.
Kuwako
M
M
Nomura
Y
Y
Suzuki
Y
Y
Shibuya
M
M
Sugita
K
K
Ito
K
K
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D019806:Cromakalim; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D012433:Ryanodine; D002110:Caffeine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium