Effects of locally generated angiotensin II on noradrenergic transmission in guinea-pig isolated atria.
The extent to which cardiac neuroeffector function may be modulated by angiotensin II (AII) generated locally from angiotensin I (AI) was investigated in guinea-pig spontaneously beating isolated atria radiolabelled with [3H]noradrenaline. AI and AII were equipotent in increasing the rate and force of atrial contractions with a threshold concentration between 0.1 and 1.0 nM. In contrast, AI was approximately twenty times less potent than AII in enhancing the stimulation-induced (S-I) efflux of radioactivity. The actions of AI and AII on rate and force of atrial contractions, as well as those on S-I efflux of radioactivity, were substantially blocked by the AII receptor antagonist saralasin. On the other hand, the converting enzyme inhibitors captopril and MK-422 selectively blocked the actions of AI without affecting those of AII. These results suggest that significant local conversion of AI to AII occurs in guinea-pig isolated atria. This locally generated AII can act on myocardial AII receptors to increase rate and force of atrial contractions, and on AII receptors located on sympathetic nerve terminals to facilitate sympathetic neurotransmission. The lower potency of AI compared to AII in modulating transmitter release, in contrast to the equal potency of the peptides in mediating chronotropic and inotropic responses, may be due to conversion of AI to AII at sites remote from the neuroeffector junction.
D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D016275:Atrial Function; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology; D009435:Synaptic Transmission
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D009638:Norepinephrine