Potency and receptors involved in coronary vasoconstriction caused by neuropeptide Y(NPY).

Aizawa, Yoshifusa; Satoh, Minoru; Aizawa, Masami; Funazaki, Toshikazu; Niwano, Shinichi; Miyajima, Seiichi; Shibata, Akira

doi:10.1536/ihj.28.891

Cited by 13 publications

(6 citation statements)

References 16 publications

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“…Strong vasoconstriction in the presence of NPY is observed in the coronary arteries from many species including humans, and the primary effect is localised in the small arteries [79,80], the result of a direct effect on vascular smooth muscle [81,82]. NPY can potentiate the effects of various mediators, including NE, histamine, 5-hydroxytryptamine, angiotensin II, prostaglandin F 2 and endothelin-1, on vascular tone [83], in some cases through an endothelium-dependent mechanism [84].…”

Section: Biological and Pathological Effects Of Npy In The Heartmentioning

confidence: 99%

NPY and Cardiac Diseases

McDermott¹,

Bell²

2007

CTMC

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Hypertension-induced left ventricular hypertrophy (LVH), along with ischemic heart disease, result in LV remodeling as part of a continuum that often leads to congestive heart failure. The neurohormonal model has been used to underpin many treatment strategies, but optimal outcomes have not been achieved. Neuropeptide Y (NPY) has emerged as an additional therapeutic target, ever since it was recognised as an important mediator released from sympathetic nerves in the heart, affecting coronary artery constriction and myocardial contraction. More recent interest has focused on the mitogenic and hypertrophic effects that are observed in endothelial and vascular smooth muscle cells, and cardiac myocytes. Of the six identified NPY receptor subtypes, Y(1), Y(2) and Y(5) appear to mediate the main functional responses in the heart. Plasma levels of NPY become elevated due to the increased sympathetic activation present in stress-related cardiac conditions. Also, NPY and Y receptor polymorphisms have been identified that may predispose individuals to increased risk of hypertension and cardiac complications. This review examines what understanding exists regarding the likely contribution of NPY to cardiac pathology. It appears that NPY may play a part in compensatory or detrimental remodeling of myocardial tissue subsequent to hemodynamic overload or myocardial infarction, and in angiogenic processes to regenerate myocardium after ischemic injury. However, greater mechanistic information is required in order to truly assess the potential for treatment of cardiac diseases using NPY-based drugs.

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Section: Biological and Pathological Effects Of Npy In The Heartmentioning

confidence: 99%

NPY and Cardiac Diseases

McDermott¹,

Bell²

2007

CTMC

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“…These latter direct effects appear to depend on high local concentrations of NPY and are most easily observed in the rat (see also Zukowska-Grojec et al, 1987). More recently, experiments performed on anaesthetized dogs have shown that local injection of NPY into coronary arteries will cause a local vasoconstriction (Aizawa et al, 1987;Martin & Patterson, 1989) or a reduction in coronary blood flow (Allen et al, 1986;Maturi et al, 1989) but effects on contractility are variable (Allen et al, 1986;Martin & Patterson, 1989). A decrease in contractility has been observed following intravenous injection of NPY in the anaesthetized rabbit (Minson et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

The effects of neuropeptide Y on myocardial contractility and coronary blood flow

Awad

Einstein

Potter

et al. 1991

British J Pharmacology

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1 This study was designed to assess the effects of exogenous neuropeptide Y (NPY) on cardiac contractility and coronary blood flow (CBF) in anaesthetized dogs and to evaluate the effect of NPY on the responses to sympathetic and parasympathetic stimulation and to inotropic agents.2 Bolus doses of NPY (500.ug), administered via the femoral vein, increased mean arterial pressure. The pressor effect was associated with reductions in heart rate, CBF and cardiac contractility. 3 The effects of NPY (500pug) on contractility and CBF were compared with that of vasopressin (VP) (1 unit). For similar reductions in CBF, NPY and VP had similar negative inotropic effects. Thus, it is likely that the negative inotropic response to NPY is not due to a direct effect of NPY on the heart muscle but is largely due to coronary vasoconstriction. 4 In the presence of NPY (500,pg, i.v.), there was an inhibition of the positive inotropic response to stimulation of the left cardiac sympathetic nerve (2 or 5Hz, 0.05 ms). NPY also inhibited the negative inotropic response and chronotropic response to vagal stimulation (2, 3 or 5 Hz, 0.05 ms). 5 Dose-response curves were obtained for the inotropic, chronotropic and pressor responses to cumulative infusions of noradrenaline (n = 6) and dobutamine (n = 6). NPY had no effect on these dose-response curves.6 The effect of NPY on the responses to salbutamol and impromidine was assessed. NPY did not alter the positive inotropic, chronotropic or depressor responses to these agonists. 7 Our results indicate that NPY has direct, postsynaptic vasoconstrictor activity and the reduction in myocardial contractility and heart rate are due to a combination of coronary vasoconstriction, baroreceptor reflex activation and presynaptic inhibition of transmitter release from sympathetic nerves. The welldocumented inhibitory effect of NPY on the chronotropic response to parasympathetic stimulation was confirmed and similar inhibition of the inotropic response to both sympathetic and parasympathetic stimulation was demonstrated. Since there was no modulation of the inotropic effects of exogenous a-and a1-adrenoceptor or H2-receptor agonists, it is concluded that the effects of NPY on myocardial contractility are exerted presynaptically.

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“…2 NPY causes considerably more long-lasting coronary vasoconstriction than NE. 19 A recent study demonstrated that NPY, released from cardiac sympathetic nerves during electrical nerve stimulation in dogs, 4 participates in the elicitation of a long-lasting coronary vasoconstriction. This may be of interest in consideration of the maintained ischemia in the recovery phase.…”

Section: Possible Role Of Npy In Ischemiamentioning

confidence: 99%

Postexercise Ischemia Is Associated With Increased Neuropeptide Y in Patients With Coronary Artery Disease

et al. 2000

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Background-Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. Methods and Results-Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was Ϫ223Ϯ20.2 V (PϽ0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (Ϫ49Ϯ8.9 V, PϽ0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was Ϫ6.0Ϯ0.77 V/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (rϭϪ0.61, Pϭ0.0005), the ST deficit at the corresponding time point (rϭϪ0.66, Pϭ0.0001), and the duration of ST-segment depression after exercise (rϭ0.42, Pϭ0.02). In contrast, no such correlations were found for NE. Conclusions-The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients. (Circulation. 2000;102:987-993.)

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Potency and receptors involved in coronary vasoconstriction caused by neuropeptide Y(NPY).

Cited by 13 publications

References 16 publications

NPY and Cardiac Diseases

NPY and Cardiac Diseases

The effects of neuropeptide Y on myocardial contractility and coronary blood flow

Postexercise Ischemia Is Associated With Increased Neuropeptide Y in Patients With Coronary Artery Disease

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