Evidence for adenosine receptor-mediated hyperpolarization in coronary smooth muscle

Sabouni, M H; Hargittai, P.T.; Lieberman, Edward M.; Mustafa, S. Jamal

doi:10.1152/ajpheart.1989.257.5.h1750

Cited by 13 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adenosine receptor-mediated hyperpolarisation of bovine and porcine coronary artery smooth muscle was reported [428,429]. Adenosine was found also to hyperpolarise cultured guinea pig coronary endothelial cells; this finding supports the hypothesis that the hyperpolarisation of the endothelium induced by adenosine released into the perivascular space of the capillaries may be conducted electrotonically to the terminal arterioles and may cause vasodilation via current flow through myoendothelial gap junctions [430].…”

Section: Coronary Blood Vesselssupporting

confidence: 54%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

View full text Add to dashboard Cite

This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

show abstract

Section: Coronary Blood Vesselssupporting

confidence: 54%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

View full text Add to dashboard Cite

show abstract

“…The membrane potential of vascular smooth muscle cells is very sensitive to the open-state probability of KATP channels ). Glibenclamide has been reported to be a specific blocker of KATP channels (see Ashcroft & Ashcroft, 1990) which binds directly to the channel protein (Bernardi, Fosset & Lazdunski, 1988;Boyd, AguilarBryan & Nelson, 1990 (Sabouni, Hargittai, Lieberman & Mustafa, 1989). In a recent study on rabbit coronary arteries (diameter, 300 ,um) it was found that both adenosine (0-3-3 Experiments with adenosine antagonists like 8-PT and adenosine uptake inhibitors like dipyridamole have often been used as tests for the adenosine hypothesis (reviewed by Berne, 1980).…”

Section: Discussionmentioning

confidence: 99%

Hypoxic vasodilatation in isolated, perfused guinea‐pig heart: an analysis of the underlying mechanisms.

Beckerath¹,

Cyrys²,

Dischner³

et al. 1991

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The mechanisms underlying hypoxic dilatation of coronary arteries were studied in isolated guinea-pig hearts perfused with physiological salt solution at 37°C. The hearts were perfused at a constant rate of 3-10 ml min-'; coronary perfusion pressure (CPP) and isovolumetric left ventricular pressure (LVP) were measured with piezoresistive transducers.2. Addition of the K+ channel opener cromakalim (500 nM) to the perfusate caused a maximal vasodilatation in beating hearts, i.e. a decrease in CPP of about 50%.Switching from normal perfusate (partial pressure of 02 (Po2), 650-700 mmHg) to hypoxic perfusate (Po2, 9-10 mmHg) caused a similar vasodilatation. Both of these effects were prevented by 2 ,um-glibenclamide, a blocker of ATP-sensitive potassium channels. Hypoxic vasodilatation was accompanied by a marked decrease in LVP, which was reduced by 56 + 22 % (mean + S.D.) in the presence of glibenclamide.3. In hearts arrested by increasing the K+ concentration of the perfusate to 15 mm, the addition of the adenosine-uptake inhibitor dipyridamole evoked a maximal vasodilatation and this was inhibited by 76+7 % in the presence of glibenclamide.4. The adenosine antagonist 8-phenyltheophylline (8-PT; 5 /M) inhibited the vasodilatation induced by dipyridamole by 88 + 10 %. In contrast, hypoxic vasodilatation was unaffected by 5 /M 8-PT. This suggests that hypoxic dilatation of coronary arteries is not mediated by release of adenosine from cardiomyocytes.5. In order to test whether release of endothelium-derived relaxing factor (EDRF) contributed to hypoxic vasodilatation we blocked EDRF synthesis with Nd-nitro-Larginine (NNA). When applied at a perfusion rate of 10 ml min-' to arrested hearts, 10 #mM-NNA increased CPP by 35 % and prolonged the delay between application of hypoxic solution and half-maximal vasodilatation from 52 + 9 to 129 + 29 s.6. Under control conditions the relation between perfusion rate and the CPP measured in the steady state was linear. In the presence of 10 /sM-NNA coronary resistance was increased more than twofold at low perfusion rates; at perfusion rates between 4 and 10 ml min-' coronary resistance decreased progressively. This change * To whom correspondence should be addressed. MS 9042 N. VON BECKERATH AND OTHERSin the pressure-flow relationship may be responsible for the alterations in the time course of hypoxic vasodilatation induced by NNA.7. In order to test whether changes in energy metabolism in coronary smooth muscle cells were responsible for hypoxic vasodilatation we blocked glycolysis by replacing the glucose in the perfusate with deoxyglucose (DOG). DOG produced a near-maximal dilatation of coronary arteries that could be reversed by 2 /Mglibenclamide but was unaffected by 5 /tM-8-PT.8. Our results suggest that adenosine can induce the opening of ATP-sensitive potassium channels in smooth muscle cells of the coronary resistance vessels, but that this is not the principal mechanism underlying hypoxic vasodilatation. It is proposed that early hypoxic dilatation of coron...

show abstract

“…It is also possible that the cell isolation method itself may reduce the size of the responses to adenosine. In a microelectrode study on bovine coronary artery 10 /ZM adenosine was found to produce a hyperpolarization of about 17 mV (Sabouni, Hargittai, Lieberman & Mustafa, 1989). Hyperpolarization will lead to decreased Ca2" entry through voltage-dependent Ca2" channels.…”

Section: The Mechanisms Of Adenosine-induced Vasodilatationmentioning

confidence: 93%

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Dart

Standen

1993

The Journal of Physiology

181

132

View full text Add to dashboard Cite

SUMMARY1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries.2. Adenosine (5-40 /SM) activated an outward current at a holding potential of 0 mV in 5 mm [K+]. and an inward current at -60 mV in 143 mm [K+] Openings became more frequent after the application of adenosine, with several levels then being detected. Openings of channels with a larger conductance were sometimes also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower estimates of unitary current than did direct measurements.5. The effect of adenosine could be mimicked by the A1 receptor agonist CCPA (2-chloro-NM-cyclopentyladenosine), while the A2 agonist CGS 21680 (2-p-(2-carboxethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) was without effect. The response to adenosine was inhibited by the A, antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by the A2antagonist CGS 15943A (5-amino-9-chloro-2-(2-furanyl)-1,2,4-triazolo[1,5-C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A1 receptor to activate K+ channels. We consider it most likely that these are ATP-dependent K+ channels. We discuss the mechanism by which K+ channel activation may lead to hyperpolarization and so vasorelaxation.

show abstract

Evidence for adenosine receptor-mediated hyperpolarization in coronary smooth muscle

Cited by 13 publications

References 0 publications

Cardiac purinergic signalling in health and disease

Cardiac purinergic signalling in health and disease

Hypoxic vasodilatation in isolated, perfused guinea‐pig heart: an analysis of the underlying mechanisms.

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Contact Info

Product

Resources

About