Premium
THROUGH AN ET‐A RECEPTOR MECHANISM ENDOTHELIN CONTRIBUTES TO SYMPATHOEXCITATORY REFLEXES DURING MYOCARDIAL ISCHEMIA
Author(s) -
Fu LiangWu,
Longhurst John
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a775-b
Subject(s) - medicine , ischemia , reflex , endothelin receptor , anesthesia , blood pressure , heart rate , phosphoramidon , cardiology , cats , receptor
Myocardial ischemia evokes sympathoexcitatory reflexes including hypertension and increases in renal sympathetic nerve activity (RSNA). Since recent studies have shown that endothelin is increased during myocardial ischemia, we hypothesized that this peptide contributes to sympathoexcitatory reflexes during ischemia. Myocardial ischemia was induced by regional coronary artery occlusion. Arterial blood pressure, heart rate, and RSNA were recorded after sinoaortic denervation and bilateral vagatomy in anesthetized cats. We observed that topical application of endothelin‐1 (ET‐1) (1–4 μg) on the heart significantly increased mean arterial blood pressure (MAP) in a dosage dependent fashion at 2 μg (135±21 vs. 153±19 mmHg) and at 4 μg (146±11 vs. 174±9 mmHg, before vs. after), but showed no increase in heart rate in five cats. We also observed that epicardial ET‐1 increased RSNA by 21% (n=4). The sympathoexcitatory responses to epicardial ET‐1 (4 μg) were abolished 5–10 min after local blockade of cardiac neural transmission with epicardial application of 2% procaine (0.2 ml) in five cats. Furthermore, BQ123 (100 μg/kg, iv), a selective ET A receptor antagonist, attenuated the brief (5 min) myocardial ischemia‐mediated reflexes (increases in MAP from 21 to 7 mmHg and the increases in RSNA from 20% to 9% (n=4)). In contrast, the reflexes tended to be repeatable during two periods of ischemia following iv injection of the vehicle (saline) for BQ123 (n=4). These data suggest that endothelin likely contributes to sympathoexcitatory reflexes during myocardial ischemia through an ET A receptor mechanism by stimulation of cardiac sympathetic afferents (Supported by NIH HL66217).