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The mechanism of acidic pH‐induced contraction in aortae from SHR and WKY rats enhanced by increasing blood pressure
Author(s) -
Furukawa KenIchi,
Komaba Junji,
Sakai Hiroyuki,
Ohizumi Yasushi
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.tb15429.x
Subject(s) - contraction (grammar) , chemistry , extracellular , medicine , vascular smooth muscle , cromakalim , verapamil , depolarization , intracellular ph , intracellular , endocrinology , aorta , nitric oxide , biophysics , channel blocker , calcium , glibenclamide , biochemistry , biology , smooth muscle , diabetes mellitus
1 Effect of pH on vascular smooth muscle contraction was analyzed by use of biochemical and pharmacological techniques. 2 In the aorta isolated from spontaneously hypertensive rats (SHR) decreasing extracellular pH (pH o ) caused a rapid acidification of intracellular pH accompanied by a pH o ‐dependent increase in tension. The contraction of the SHR aorta was remarkable compared with that of the Wistar Kyoto rat (WKY) aorta. 3 Removal of NH 4 Cl caused a transient decrease in intracellular pH followed by a marked increase in tension. 4 Both contraction and intracellular Ca 2+ mobilization induced by acidic pH o were markedly inhibited by removal of extracellular Ca 2+ , verapamil and adenosine, whereas these were not affected by tetrodotoxin or Gd 3+ , a stretch‐activated cation channel blocker. Furthermore, cromakalim (a K + channel opener) inhibited acidic pH o ‐induced contraction (APIC). 5 Acidic pH o induced a depolarization of cultured smooth muscle cells from SHR aorta. 6 Blood pressure elevated with increasing age of WKY and SHR accompanied by an increase in APIC. Feeding WKY with N G ‐nitro‐L‐arginine, an inhibitor of nitric oxide synthases caused a marked elevation of their blood pressure followed by an increase in APIC. 7 These results suggest that APIC is caused by Ca 2+ influx mediated through the activation of voltage‐sensitive Ca 2+ channels mainly due to acidic pH o ‐induced depolarization of the plasma membrane of smooth muscle cells. It is also suggested that APIC is strengthened by the elevation of blood pressure.