Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

Tomohiko Ai, Minoru Horie, Kazuhiko Obayashi, Shigetake Sasayama

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Abstract

To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca2+ currents (I(Ca,L)) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I(Ca,L) was recorded by a step-pulse protocol after eliminating K+ conductances (internal Cs+ plus tetraethylammonium chloride and K+-free extracellular solution). A-II (100 nM) did not affect basal I(Ca,L), but inhibited I(Ca,L) that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I(Ca,L) was completely blocked by A- II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT1) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I(Ca,L) enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I(Ca,L) enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT1 receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.

Original languageEnglish (US)
Pages (from-to)168-174
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume436
Issue number2
DOIs
StatePublished - Jun 13 1998

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Keywords

  • Angiotensin-II
  • L-type Ca current
  • PTX-sensitive G proteins
  • Protein kinase A
  • cAMP

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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