The Mechanism of the Contractile Action of Angiotensin II

Abstract

The mechanism of the contractile action of angiotensin II was investigated on the rat descending colon and the effect of all experimental treatments were compared with their effect upon equivalent responses to PGE2 and KCl. Exposure to Ca2+ -free Tyrode caused a ‘greater reduction of responses to angiotensin than of responses to PGE2 and KCl. An increase in [Ca2]e from 1.8 to 3.6mM potentiated the responses to angiotensin and KCl and a further increase to either 7.2mM or 10.8mM potentiated the responses £0 angiotensin and PGE2 but reduced responses to KCl. Ca 2+-free Tyrode with SKF525A or verapamil abolished the responses to angiotensin, PGE2 and KCl. Reintroduction of Ca + caused incomplete recovery of responses to angiotensin and PGE2 but no recovery of responses to KC1. Reduction of {na+}e increased the initial response to angiotensin and PGE2 but reduced subsequent responses while responses to KCl were consistently increased. Isoprenaline, theophylline and dibutyryl cyclic AMP caused a greater reduction in responses to angiotensin and PGE) than KCl. Indomethacin (50uM) reduced the responses to all three spasmogens. Contraction and membrane electrical activity were measured by the sucrose-gap method with KCl as a control spasmogen. Contractions of longitudinal muscle of the rat descending colon to angiotensin were associated with small membrane depolarizations <5mV) which were dependent upon extracellular Ca2* and Na® and unaffected by verapamil. Contractions of guinea-pig taenia coli to angiotensin were associated with membrane depolarization and an increase in spike size and frequency. The spikes were dependent on extracellular Ca 2+ and reduced by verapamil but the membrane depolarization was dependent on extracellular Na* and unaffected by verapamil. Angiotensin and KCl increased cellular 45ca uptake measured by the lanthanum technique. The increase due to KC1 but not to Angiotensin was abolished by verapamil. The findings suggest that the contractile action of angiotensin upon smooth muscle is direct and may involve Ca2+/Na+ movement. Key words: Angiotensin, smooth muscle, calcium-antagonists.