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

Abstract

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.

Effects of Neuropeptide Y on Intrarenal Hemodynamics, Plasma Renin Activity and Urinary Sodium Excretion in Rats

“…NPY might have either no or a positive chronotropic effect [27,28]. Similar observations have been made in innervated heart preparations [29][30][31]. The situation is particularly complex in intact animals.…”

Neuropeptide Y in human hand veins: Pharmacologic characterization and interaction with cyclic guanosine monophosphate-dependent venodilators in vivo*

“…& THERAPEUTICS DECEMBER 1995 independent,26 and they largely depend on the origin of the vessel and may be absent in certain vascular beds. 22,27 In particular, in vitro potentiation in veins may be absent or limited to certain agonists, whereas the interaction with human neuropeptide Y, irrespective of the agonist, may be substantial and not selective in the corresponding arteries.2"'23 Therefore many of the numerous vascular effects of human neuropeptide Y increase vascular tone directly or indirectly through an increased responsiveness of the vasculature to circulating vasopressors. In humans, plasma concentrations of human neuropeptide Y increase with age and after reflex sympathetic stimulation induced by physical exercise,28-31 lower body negative pressure," standing,72 or cold pressure testing.…”

Neuropeptide Y is a prejunctional inhibitor of vagal but not sympathetic inotropic responses in guinea‐pig isolated left atria

“…Previous findings from investigations into direct inotropic effects of NPY on myocardial contractility are confounding and often contradictory depending on the species and preparation examined. NPY has been shown to have negative inotropic effects in vivo ( Allen et al ., 1986 ; Minson et al ., 1987 ; 1989 ; 1990 ; Zukowska‐Grojec et al ., 1987 ; Awad et al ., 1991 ) and in vitro ( Allen et al ., 1983 ; Franco‐Cereceda et al ., 1985 ; Rioux et al ., 1986 ; Jolly et al ., 1991 ) however, these decreases in contractility are suggested to be secondary to impaired myocardial perfusion and ischaemia. When the effects of NPY are examined in preparations devoid of the confounding effects of changes in myocardial perfusion, there is still disagreement in results.…”