Abstract:
:Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists on baseline and atrial stretch-induced immunoreactive ANP (IR-ANP) and immunoreactive N-terminal ANP (IR-NT-ANP) release in vivo by using BQ-123 (ETA receptor antagonist), bosentan (ETA and ETB receptor antagonist), and losartan (AT1 receptor antagonist). Intravenous administration of BQ-123 had no significant effect on baseline hemodynamics in conscious rats, whereas bosentan (10 mg/kg) and losartan (10 mg/kg) decreased slightly (4 to 7 mm Hg, P < .05 to .001) the mean arterial pressure. Both the ETA receptor antagonist BQ-123 and ETA/ETB receptor antagonist bosentan decreased plasma ANP and NT-ANP responses to volume load (P < .05 to .001), whereas the AT1 receptor antagonist losartan had no significant effect on this response. The relative increase in plasma IR-ANP corresponding to a 3 mm Hg increase in right atrial pressure was 2.7-fold in the vehicle-treated group. BQ-123 (0.3 and 1.0 mg/kg) decreased this response 2.5- and 2.1-fold (P < .05); bosentan (3 and 10 mg/kg), 1.7-fold (P < .001) and 1.9-fold (P < .05); and bosentan (10 mg/kg)+losartan (10 mg/kg), 1.6-fold (P < .001). The responses in plasma IR-NT-ANP decreased simultaneously. These results indicate that combined inhibition of ETA/B and AT1 receptors almost completely blocks ANP response to acute volume load. Therefore, our study shows that endogenous paracrine and/or autocrine factors liberated in response to atrial wall stretch rather than myocyte stretch itself are responsible for the activation of ANP peptide secretion in response to acute volume load. Our results also show that ETA receptors are more important in the regulation of mechanical stretch-induced changes in cardiac hormone secretion than AT1 receptors.
journal_name
Circ Resjournal_title
Circulation researchauthors
Leskinen H,Vuolteenaho O,Ruskoaho Hdoi
10.1161/01.res.80.1.114subject
Has Abstractpub_date
1997-01-01 00:00:00pages
114-23issue
1eissn
0009-7330issn
1524-4571journal_volume
80pub_type
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