Chronotropic and vasodilatory responses to adenosine and isoproterenol in mouse heart: effects of adenosine A1 receptor overexpression.
Chronotropic and vasodilatory responses to adenosine and isoproterenol in mouse heart: effects of adenosine A1 receptor overexpression.
复制标题
小鼠心脏对腺苷和异丙肾上腺素的变时性和血管舒张反应：腺苷 A1 受体过度表达的影响。
DOI：
10.1046/j.1440-1681.2000.03218.x
复制
发表时间：
2000
影响因子：
2.9
通讯作者：
Matherne,GP
中科院分区：
文献类型：
--
作者：
Headrick,JP;Gauthier,NS;Morrison,RR;Matherne,GP
1. Chronotropic and vasodilatory effects of adenosine receptor activation with 2‐chloroadenosine (2‐ClAdo) and β‐adrenoceptor activation with isoproterenol were studied in wild‐type murine hearts and transgenic hearts overexpressing the A1adenosine receptor.2. Treatment of wild‐type hearts with 2‐ClAdo induced bradycardia (pEC506.4±0.2) and vasodilatation (pEC507.9±0.1; minimal resistance 2.2±0.2 mmHg/mL per min per g). The A1receptor‐mediated bradycardia was 20‐fold more sensitive in transgenic hearts (pEC507.7±0.2), whereas coronary vasoactivity of 2‐ClAdo was unaltered (pEC507.6±0.1).3. β‐Adrenoceptor stimulation with isoproterenol increased heart rate (pEC508.5±0.2; maximal rate 594±23 b.p.m.) and produced vasodilation (pEC508.7±0.1; minimal resistance 1.7±0.2 mmHg/mL per min per g) in wild‐type hearts. Treatment with 10 IU/mL adenosine deaminase increased the magnitude of the tachycardia (maximal rate 653±27 b.p.m.) without altering potency (pEC508.5±0.1). Antagonism of A1receptors with 10 nmol/L 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) produced a comparable increase in the magnitude of the chronotropic response (maximal rate 695±26 b.p.m.) without altering potency (pEC508.3±0.1).4. Isoproterenol‐mediated vasodilatation was unaltered by transgenic A1receptor overexpression. Overexpression of A1receptors significantly reduced the maximal heart rate during β‐adrenoceptor stimulation by 35% (to 381±28 b.p.m.) without altering potency (pEC508.4±0.2). At 10 nmol/L, DPCPX increased the magnitude of the chronotropic response to isoproterenol in transgenic hearts (maximal heart rate 484±36 b.p.m.) without altering potency (pEC508.3±0.2).5. The data show that transgenic A1receptor overexpression selectively sensitizes the cardiovascular A1receptor response and that A1receptor activation by endogenous adenosine depresses the magnitude, but not potency, of the β‐adrenoceptor‐mediated chronotropic response in mouse heart. The A1receptor‐mediated depression of β‐adrenoceptor responsiveness is non‐competitive (reduced response magnitude with no change in sensitivity). This indicates that A1receptor activation non‐competitively inhibits effector mechanisms activated by β‐adrenoceptors (e.g. adenylate cyclase) and/or A1receptors activate unrelated but opposing mechanisms. This inhibitory response may have physiological importance during periods of sympathetic stimulation of cardiac work.
