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 cy toplasmic [Ca2+] (Ca-i) and muscle tension in rat mesenteric resistanc e arteries induced by norepinephrine (NE) and caffeine. Both ryanodine and thapsigargin markedly inhibited the increase in Ca-i and contract ile responses to caffeine in physiological saline and to NE and caffei ne in calcium-free conditions. In contrast, peak responses to potassiu m depolarisation and NE in physiological saline appeared little affect ed, 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 Ca-i or the Ca2+ se nsitivity of contraction under depolarized conditions. The NE concentr ation-response relationship was not significantly altered after ryanod ine or thapsigargin. Ryanodine and thapsigargin inhibit the release of intracellular Ca2+ stores by NE and caffeine. Inhibition of release o f intracellular Ca2+ by NE has only slight effects on contractile resp onses of mesenteric resistance arteries when extracellular Ca2+ is pre sent.