Angiotensin stimulates Ca2(+)-dependent action potentials in cultured smooth muscle cells.
The steady-state angiotensin II response was measured in primary cultures of reaggregated vascular smooth muscle cells derived from rat aorta by use of intracellular microelectrode recording of membrane potentials. Angiotensin II (10(-9)-10(-6) M) produced a depolarization which triggered a single action potential, consisting of a spike plus plateau. In addition, angiotensin II prolonged the action potential plateau and lowered input resistance. The angiotensin II-induced action potentials and the action potential plateau prolongation were inhibited by verapamil. Saralasin blocked the occurrence of angiotensin II-induced action potentials and reversed the increase in action potential duration provoked by angiotensin II. Saralasin, in the absence of angiotensin II, exhibited agonistic activity which was manifest by plateau prolongation. Therefore, angiotensin II, through interaction of the peptide with its receptor, depolarizes cultured vascular smooth muscle cells and prolongs the calcium-dependent action potentials. These effects could be mediated by the known ability of angiotensin II to stimulate production of inositol trisphosphate and diacylglycerol, and activation of protein kinase C.
Johns
D W
DW
Department of Internal Medicine, University of Virginia, Charlottesville 22908.
Sperelakis
N
N
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000804:Angiotensin II; D014700:Verapamil; D012504:Saralasin; D002118:Calcium; D009638:Norepinephrine