Inotropic effects of ETB receptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Leite Moreira, AF (Author) FMUP; Bras Silva, C (Author) FCNAUP

Journal

Title: American Journal of Physiology - Heart and Circulatory Physiology

Vol. 287 No. 6

Pages: H1194-H1199

ISSN: 0363-6135

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 33 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-000-8K7

DOI: 10.1152/ajpheart.00563.2003

Abstract (EN): Endothelin (ET)-1 acts on ETA and ETB receptors. The latter include ETB1 (endothelial) and ETB2 (muscular) subtypes, which mediate opposite effects on vascular tone. This study investigated, in rabbit papillary muscles (n = 84), the myocardial effects of ETB stimulation. ET-1 (10(-9) M) was given in the absence or presence of BQ-123 (ETA antagonist). The effects of IRL-1620 (ETB1 agonist, 10(-10) - 10(-6) M) or sarafotoxin S6c (ETB agonist, 10(-10) - 10(-6) M) were evaluated in muscles with intact or damaged endocardial endothelium (EE); intact EE, in the presence of N-G-nitro-L-arginine (L-NNA); and intact EE, in the presence of indomethacin ( Indo). Sarafotoxin S6c effects were also studied in the presence of BQ-788 (ETB2 antagonist). ET-1 alone increased 64 +/- 18% active tension (AT) but decreased it by 4 +/- 2% in the presence of BQ-123. In muscles with intact EE, sarafotoxin S6c alone did not significantly alter myocardial performance. Sarafotoxin S6c (10(-6) M) increased, however, AT by 120 +/- 27% when EE was damaged and by 39 +/- 8% or 23 +/- 6% in the presence of L-NNA or Indo, respectively. In the presence of BQ-788, sarafotoxin S6c decreased AT ( 21 +/- 3% at 10(-6) M) in muscles with intact EE, an effect that was abolished when EE was damaged. IRL-1620 also decreased AT ( 22 +/- 3% at 10(-6) M) in muscles with intact EE, an effect that was abolished when EE was damaged or in the presence of L-NNA or Indo. In conclusion, the ETB-mediated negative inotropic effect is presumably due to ETB1 stimulation, requires an intact EE, and is mediated by NO and prostaglandins, whereas the ETB-mediated positive inotropic effect, observed when EE was damaged or NO and prostaglandins synthesis inhibited, is presumably due to ETB2 stimulation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6