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Possible mechanism of the potent vasoconstrictor actions of ryanodine on femoral arteries from spontaneously hypertensive rats
Author(s) -
Asano Masahisa,
Kuwako Miho,
Nomura Yukiko,
Ito Kaoru M.,
Ito Katuaki,
Uyama Yoshiaki,
Imaizumi Yuji,
Watanabe Minoru
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15501.x
Subject(s) - ryanodine receptor , medicine , contraction (grammar) , endocrinology , verapamil , nifedipine , chemistry , muscle contraction , caffeine , calcium , vascular smooth muscle , smooth muscle
1 The Ca 2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of ryanodine that removes the function of SR, on tension and cellular Ca 2+ level were assessed in endothelium‐denuded strips of femoral arteries from 13‐week‐old SHR and normotensive Wistar‐Kyoto rats (WKY). 2 The addition of ryanodine to the resting strips caused a concentration‐dependent contraction in SHR. This contraction was extremely small in WKY. In the presence of 10 −5 m ryanodine, caffeine (20 mM) failed to cause a further contraction in SHR, but it caused a small contraction in WKY. After washout of the strips with a Krebs solution, the resting tone was greatly elevated in SHR when compared with WKY. 3 The elevated resting tone in SHR strips was abolished by 10 −7 m nifedipine. The ryanodine‐induced contraction was also abolished by 10 −7 m nifedipine. Nifedipine itself caused a relaxation from the resting tone of SHR strips, suggesting the maintenance of myogenic tone. 4 In strips preloaded with fura‐PE3, the addition of 10 −5 m ryanodine caused a large and moderate elevation of cytosolic Ca 2+ level ([Ca 2+ ] i ) in SHR and WKY, respectively. After washout, the resting [Ca 2+ ] i was greatly elevated in SHR. The ryanodine‐induced elevation of [Ca 2+ ] i was decreased by 5 × 10 −6 m verapamil in SHR. Verapamil itself caused a decrease in resting [Ca 2+ ] i which was significantly greater in SHR than in WKY, and caused a relaxation only in SHR. 5 The resting Ca 2+ influx in arteries measured by a 5 min incubation with 45 Ca was significantly increased in SHR when compared with WKY. The resting Ca 2+ influx was not increased by 10 −5 m ryanodine in both SHR and WKY. The net cellular Ca 2+ uptake in arteries measured by a 30 min incubation with 45 Ca was decreased by 10 −5 m ryanodine in both strains. 6 The resting Ca 2+ influx was decreased by 10 −7 m nifedipine in the SHR artery, but it was unchanged in the WKY artery. 7 These results suggest that (1) the Ca 2+ influx via L‐type voltage‐dependent Ca 2+ channels was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca 2+ influx was buffered by Ca 2+ uptake into the SR and some Ca 2+ reached the myofilaments resulting in the maintenance of the myogenic tone, and (3) therefore the functional removal of SR by ryanodine caused a potent contraction in this artery.