Endothelin acts as a paracrine regulator of stretch-induced atrial natriuretic peptide release.
Several lines of evidence suggest a paracrine regulatory role for endothelin (ET) in the release of atrial natriuretic peptide (ANP). To investigate this possibility, we used the ET A-type receptor (ETA-R) competitive inhibitor cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123) in isolated perfused atria to determine the effect of endogenously produced ET on the release of ANP. Initially, we found that high pressure (8-10 mmHg) increased the mean ANP secretion rate by 117.3 +/- 21.2% (P < 0.05). Next, we found that at high pressure 50 nM of exogenously applied ET significantly augmented the stretch-induced release of ANP (P < 0.05) and that this response could be significantly attenuated in a dose-dependent manner by 1 and 3 microM BQ-123 (P < 0.05). These experiments proved the efficacy of the inhibitor in our model. Subsequently, we found that the stretch-induced release of ANP was significantly reduced to 51.5 +/- 13.0 and 22.3 +/- 11.8% by 1 and 3 microM BQ-123, respectively (P < 0.05). Because the perfused atria model eliminates systemic cardiovascular effects, allows control and direct recording of the intra-atrial pressure, and preserves the potential endothelium-myocyte control system, we conclude that the stretch-induced release of ANP is partially regulated by ET and that the ET is locally produced and constitutes a paracrine control system.
Skvorak
J P
JP
Department of Physiology and Biophysics, University of South Florida College of Medicine, Tampa 33612, USA.
Nazian
S J
SJ
Dietz
J R
JR
D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010456:Peptides, Cyclic / Q000494:pharmacology; D010812:Physical Stimulation; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D009320:Atrial Natriuretic Factor; C072247:cyclo(Trp-Asp-Pro-Val-Leu)