Abstract
Myocardial hypoperfusion is accompanied by concomitant increases in adenosine and endothelin-1 (ET-1) production, but the vasodilatory effect of adenosine prevails over that of ET-1. Therefore, we hypothesized that adenosine-induced or ischemic preconditioning reduces the vasoconstrictive effect of ET-1. Coronary arteriolar diameter in vivo was measured using fluorescence microangiography in anesthetized open-thorax dogs. ET-1 (5 ng·kg-1·min-1 administered intracoronary, n = 10) induced progressive constriction over 45 min [25 ± 6% (SE)]. The constriction was blocked by preconditioning with adenosine (25 μg·kg-1·min-1 administered intracoronary) for 20 min and 10 min of washout (n = 10) or attenuated by ischemic preconditioning (four 5-min periods of ischemia, 9 ± 5% at 45 min). To investigate the receptor involved in this process, coronary arterioles (50-150 μm) were isolated and pressurized at 60 mmHg in vitro. The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 μM) for 20 min and 10 min of washout (n = 11). Blockade of A2 receptors [8-(3-chlorostyryl)caffeine, 1 μM, n = 9] but not A1 receptors (8-cyclopentyl-1,3-dipropylxanthine, 100 nM, n = 7) prevented this shift. These results suggest that adenosine confers a vascular preconditioning effect, mediated via the A2 receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 279 |
| Issue number | 6 48-6 |
| State | Published - Dec 1 2000 |
| Externally published | Yes |
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Keywords
- Coronary blood flow
- Coronary microcirculation
- Ischemic preconditioning
- Vasoconstriction
- Vasodilation
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
Adenosine preconditions against endothelin-induced constriction of coronary arterioles. / Merkus, Daphne; Stepp, David W; Jones, Deron W.; Nishikawa, Yasuhiro; Chilian, William M.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 279, No. 6 48-6, 01.12.2000.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adenosine preconditions against endothelin-induced constriction of coronary arterioles
AU - Merkus, Daphne
AU - Stepp, David W
AU - Jones, Deron W.
AU - Nishikawa, Yasuhiro
AU - Chilian, William M.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - Myocardial hypoperfusion is accompanied by concomitant increases in adenosine and endothelin-1 (ET-1) production, but the vasodilatory effect of adenosine prevails over that of ET-1. Therefore, we hypothesized that adenosine-induced or ischemic preconditioning reduces the vasoconstrictive effect of ET-1. Coronary arteriolar diameter in vivo was measured using fluorescence microangiography in anesthetized open-thorax dogs. ET-1 (5 ng·kg-1·min-1 administered intracoronary, n = 10) induced progressive constriction over 45 min [25 ± 6% (SE)]. The constriction was blocked by preconditioning with adenosine (25 μg·kg-1·min-1 administered intracoronary) for 20 min and 10 min of washout (n = 10) or attenuated by ischemic preconditioning (four 5-min periods of ischemia, 9 ± 5% at 45 min). To investigate the receptor involved in this process, coronary arterioles (50-150 μm) were isolated and pressurized at 60 mmHg in vitro. The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 μM) for 20 min and 10 min of washout (n = 11). Blockade of A2 receptors [8-(3-chlorostyryl)caffeine, 1 μM, n = 9] but not A1 receptors (8-cyclopentyl-1,3-dipropylxanthine, 100 nM, n = 7) prevented this shift. These results suggest that adenosine confers a vascular preconditioning effect, mediated via the A2 receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.
AB - Myocardial hypoperfusion is accompanied by concomitant increases in adenosine and endothelin-1 (ET-1) production, but the vasodilatory effect of adenosine prevails over that of ET-1. Therefore, we hypothesized that adenosine-induced or ischemic preconditioning reduces the vasoconstrictive effect of ET-1. Coronary arteriolar diameter in vivo was measured using fluorescence microangiography in anesthetized open-thorax dogs. ET-1 (5 ng·kg-1·min-1 administered intracoronary, n = 10) induced progressive constriction over 45 min [25 ± 6% (SE)]. The constriction was blocked by preconditioning with adenosine (25 μg·kg-1·min-1 administered intracoronary) for 20 min and 10 min of washout (n = 10) or attenuated by ischemic preconditioning (four 5-min periods of ischemia, 9 ± 5% at 45 min). To investigate the receptor involved in this process, coronary arterioles (50-150 μm) were isolated and pressurized at 60 mmHg in vitro. The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 μM) for 20 min and 10 min of washout (n = 11). Blockade of A2 receptors [8-(3-chlorostyryl)caffeine, 1 μM, n = 9] but not A1 receptors (8-cyclopentyl-1,3-dipropylxanthine, 100 nM, n = 7) prevented this shift. These results suggest that adenosine confers a vascular preconditioning effect, mediated via the A2 receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.
KW - Coronary blood flow
KW - Coronary microcirculation
KW - Ischemic preconditioning
KW - Vasoconstriction
KW - Vasodilation
UR - http://www.scopus.com/inward/record.url?scp=0034536781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034536781&partnerID=8YFLogxK
M3 - Article
C2 - 11087209
AN - SCOPUS:0034536781
VL - 279
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 6 48-6
ER -