Inhibition of norepinephrine and caffeine-induced activation by ryanodine and thapsigargin in rat mesenteric arteries.
We examined the effects of ryanodine and thapsigargin on changes in cytoplasmic [Ca2+] (Cai) and muscle tension in rat mesenteric resistance arteries induced by norepinephrine (NE) and caffeine. Both ryanodine and thapsigargin markedly inhibited the increase in Cai and contractile responses to caffeine in physiological saline and to NE and caffeine in calcium-free conditions. In contrast, peak responses to potassium depolarisation and NE in physiological saline appeared little affected, although time taken to achieve 50% of peak response after addition of NE was slowed after ryanodine and thapsigargin treatment. Neither ryanodine nor thapsigargin altered resting tone or Cai or the Ca2+ sensitivity of contraction under depolarized conditions. The NE concentration-response relationship was not significantly altered after ryanodine or thapsigargin. Ryanodine and thapsigargin inhibit the release of intracellular Ca2+ stores by NE and caffeine. Inhibition of release of intracellular Ca2+ by NE has only slight effects on contractile responses of mesenteric resistance arteries when extracellular Ca2+ is present.
Garcha
R S
RS
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, England.
Hughes
A D
AD
D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000008:administration & dosage / Q000494:pharmacology*; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*; D019284:Thapsigargin; D014655:Vascular Resistance / Q000187:drug effects
D013729:Terpenes; D012433:Ryanodine; D002110:Caffeine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine