Selective inhibition of angiotensin-induced contractions of smooth muscle by indomethacin

1The role of prostaglandins in contractions of the guinea-pig ileum evoked either directly by acetylcholine or indirectly by angiotensin and by coaxial stimulation has been investigated. 2 Prostaglandin E2 in low concentration (6 nM) slightly augmented both types of contraction. Indomethacin, an inhibitor of prostaglandin synthesis, markedly reduced the indirectly evoked contractions but did not affect contractions in response to acetylcholine. The addition of prostaglandin E2 to the preparation treated previously with indomethacin restored the effect of indirect stimulation. 3 The pretreatment of the preparation with guanethidine or a-methyl-p-tyrosine prevented the inhibitory effect of indomethacin on indirectly evoked contractions. Prostaglandin E2 addition to such preparations considerably augmented both types of contraction. 4 The stimulation of non-cholinergic, non-adrenergic inhibitory nerves in the taenia coli and ileum preparations evoked hyperpolarization and relaxation of the preparations followed by action potentials and contraction. These responses were not changed by indomethacin pretreatment and prostaglandin E2, but rebound contraction was sometimes augmented by the prostaglandin. 5 Two mechanisms for the effects of prostaglandin E2 are suggested: a direct effect on smooth muscle, and an indirect action through the sympathetic nerves which by release of noradrenaline affect the acetylcholine release from parasympathetic nerve endings.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Modulating Role of Prostaglandins in Contractions of the Guinea‐pig Ileum

Kadlec

Mašek

Šeferna

1974

“…Use of inhibitors of prostaglandin synthesis has led to the concept that prostaglandins attenuate angiotensin's pressor effects (Aiken, 1974). However, in some vascular smooth muscle preparations, experiments with synthesis inhibitors suggested that prostaglandins potentiate angiotensin (Chong & Downing, 1973). Explanations for this discrepancy may involve considerations of the variability in reactivity of different smooth muscles and/or nonspecific effects of prostaglandin synthetase inhibitors (Aboulafia, Mendes, Mujamato, Paiva & Paiva, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…Other investigators observed actions of these agents on angiotensin's effects. Chong & Downing (1973), BaudouinLegros, Meyer & Worcel (1974), and Aboulafia et al (1976) observed antagonism of angiotensin by indomethacin in isolated smooth muscle. Chong & Downing suggested that the effect was caused by inhibition of prostaglandin synthesis.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Receptors in Bovine Umbilical Artery and Their Inhibition by Nonsteroidal Anti‐inflammatory Drugs

Goodfriend

Simpson

1981

“…Other studies have generally indicated a facilitatory, rather than inhibitory role for prostaglandins in cholinergic transmission in the guinea-pig isolated ileum. Thus various studies show that indirectly evoked contractions of the guinea-pig ileum such as those induced by nicotine, angiotensin or transmural stimulation are inhibited by cyclo-oxygenase inhibitors and the inhibited responses are restored by low concentrations of prostaglandins (Chong & Downing, 1973;Bennett et al, 1975a;Sokunbi, 1979).…”

Section: Introductionmentioning

confidence: 99%

Cyclo‐oxygenase inhibitors antagonize indirectly evoked contractions of the guinea‐pig isolated ileum by inhibiting acetylcholine release

Okpako¹,

Taiwo²

1984

1The effects of indomethacin, sodium meclofenamate and ketoprofen on the contractile responses of the guinea-pig isolated ileum to directly and indirectly evoked stimuli were investigated. The effects of the cyclo-oxygenase inhibitors on acetylcholine (ACh) release from plexus containing longitudinal muscle strips were also studied. 2 The cyclo-oxygenase inhibitors reduced contractile responses to transmural stimulation (TMS) and nicotine at concentrations which had no effect on ACh-induced contractions.3 In whole ileum preparations (WIP) indomethacin and ketoprofen (40jig ml-') reduced TMS responses by 17 ± 1.8% and 12 ± 1.8% (n = 6), respectively (30 min incubation). In longitudinal muscle strips (LMS) in which Auerbach's plexus is exposed, indomethacin and ketoprofen (1 ig ml-1) reduced TMS responses by 28±2.3% and 34±2.7% (n =6), respectively (10 min incubation). Thus the cyclo-oxygenase inhibitors were up to 80 times more effective in LMS than in WIP. The drugs were similarly more effective in blocking nicotine contractions in LMS than in WIP. 4 The cyclo-oxygenase inhibitors reduced basal and stimulated ACh release from LMS. For example, indomethacin (1 ig ml'-) reduced stimulated ACh release by 35% after 10 min incubation. The percentage inhibition increased to 79% after 40 min incubation (n = 6). 5 Prostaglandin E2 (PGE2) (0.1-2.5 ng ml-') restored the contractile responses and ACh release depressed by the cyclo-oxygenase inhibitors but not the contractile responses depressed by atropine.PGF2. had no effect on mechanical responses or ACh release depressed by the cyclo-oxygenase inhibitors. 6 It is concluded that the cyclo-oxygenase inhibitors studied reduced responses to transmural stimulation and nicotine by inhibiting ACh release. The site of action is the postganglionic parasympathetic nerve. 7 It is suggested that the reason why previous investigators needed to use high doses of cyclooxygenase inhibitor in the ileum is because the action of the inhibitor is limited by diffusion barriers. There was no evidence to support the view that there is more than one pool of cyclo-oxygenase in guinea-pig gut.